Background/aim: Ribosomal proteins have been shown to perform unique extraribosomal functions in cell apoptosis and other biological processes. Ribosomal protein L8 (RPL8) not only has important nonribosomal regulatory functions but also participates in the oncogenesis and development of tumors. However, the specific biological functions and pathways involved in this process are still unknown. Materials and methods: RPL8 was overexpressed (RPL8-OE) in HeLa cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transcriptome sequencing was performed to analyze the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs) by RPL8-OE, both of which were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. Results: RPL8-OE inhibited cell proliferation and promoted cell apoptosis. RPL8 regulated the differential expression of many oncogenic genes and the occurrence of RASEs. Many DEGs and RASE genes (RASGs) were enriched in tumorigenesis and tumor progressionrelated pathways, including angiogenesis, inflammation, and regulation of cell proliferation. RPL8 could regulate the RASGs enriched in the negative regulation of apoptosis, consistent with its proapoptosis function. Furthermore, RPL8 may influence cancer-related DEGs by modulating the alternative splicing of transcription factors. Conclusion: RPL8 might affect the phenotypes of cancer cells by altering the transcriptome profiles, including gene expression and splicing, which provides novel insights into the biological functions of RPL8 in tumor development.
{"title":"Ribosomal protein L8 regulates the expression and splicing pattern of genes associated with cancer-related pathways","authors":"LEILEI XU, GUI YANG, BIN SONG, DONG CHEN, Akbar. Yunus, JIANGTAO CHEN, XIAOGANG YANG, ZHENG TIAN","doi":"10.55730/1300-0152.2666","DOIUrl":"https://doi.org/10.55730/1300-0152.2666","url":null,"abstract":"Background/aim: Ribosomal proteins have been shown to perform unique extraribosomal functions in cell apoptosis and other biological processes. Ribosomal protein L8 (RPL8) not only has important nonribosomal regulatory functions but also participates in the oncogenesis and development of tumors. However, the specific biological functions and pathways involved in this process are still unknown. Materials and methods: RPL8 was overexpressed (RPL8-OE) in HeLa cells. MTT assay and flow cytometry were used to detect cell proliferation and apoptosis, respectively. Transcriptome sequencing was performed to analyze the differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs) by RPL8-OE, both of which were validated by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. Results: RPL8-OE inhibited cell proliferation and promoted cell apoptosis. RPL8 regulated the differential expression of many oncogenic genes and the occurrence of RASEs. Many DEGs and RASE genes (RASGs) were enriched in tumorigenesis and tumor progressionrelated pathways, including angiogenesis, inflammation, and regulation of cell proliferation. RPL8 could regulate the RASGs enriched in the negative regulation of apoptosis, consistent with its proapoptosis function. Furthermore, RPL8 may influence cancer-related DEGs by modulating the alternative splicing of transcription factors. Conclusion: RPL8 might affect the phenotypes of cancer cells by altering the transcriptome profiles, including gene expression and splicing, which provides novel insights into the biological functions of RPL8 in tumor development.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mitochondria are organelles that serve as the powerhouses for cellular bioenergetics in eukaryotic cells. It is responsible for mitochondrial adenosine triphosphate (ATP) generation, cell signaling and activity, calcium balance, cell survival, proliferation, apoptosis, and autophagy. Mitochondrial transplantation is a promising disease therapy that involves the recovery of mitochondrial dysfunction using isolated functioning mitochondria. The objective of the present article is to provide current knowledge on natural mitochondrial transfer processes, in vitro and in vivo applications of mitochondrial transplantation, clinical trials, and challenges associated with mitochondrial transplantation.
{"title":"Mitochondrial transplantation and transfer: The promising method for diseases","authors":"GÖKHAN BURÇİN KUBAT","doi":"10.55730/1300-0152.2665","DOIUrl":"https://doi.org/10.55730/1300-0152.2665","url":null,"abstract":"Mitochondria are organelles that serve as the powerhouses for cellular bioenergetics in eukaryotic cells. It is responsible for mitochondrial adenosine triphosphate (ATP) generation, cell signaling and activity, calcium balance, cell survival, proliferation, apoptosis, and autophagy. Mitochondrial transplantation is a promising disease therapy that involves the recovery of mitochondrial dysfunction using isolated functioning mitochondria. The objective of the present article is to provide current knowledge on natural mitochondrial transfer processes, in vitro and in vivo applications of mitochondrial transplantation, clinical trials, and challenges associated with mitochondrial transplantation.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"24 7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
XIAN TANG, JUN GAO, JINPENG HUANG, CHENJUAN ZHANG, HONGWEI LIU, JIE WEI
Background/aim: Obesity is the fifth largest risk factor of death in the world. The ceramide produced by obesity is closely related to insulin resistance (IR) caused by obesity. At present, the commercially available weight loss products have large side effects and limited therapeutic effects. Therefore, it is particularly important to find effective natural nontoxic products to treat obesity and explore its possible pathways and mechanisms. Materials and methods: In this paper, a high-fat diet (HFD) mice model was established by intragastric administration of high-fat emulsion to investigate the intervention effect of Gooseberry anthocyanins (GA) on IR in HFD mice. We used molecular docking technology to find the binding sites and binding energy of anthocyanins on CerS6. Real-time PCR was used to detect the effect of GA on the expression of IL-6 and TNF-α mRNA in HFD mice. The expression of S1P/Cer signaling pathway in HFD mice with IR was detected by Western Blot. Results: The results showed that GA could effectively inhibit visceral fat, liver index, the level of TC, TG and the level of LDL-C (p < 0.05), and improved HDL-C, GSH-Px and SOD (p < 0.05). GA decreased the level of insulin sensitivity index from -5.15 to -4.54 and improved insulin sensitivity and IR in HFD mice. The binding energy of anthocyanins on CerS6 was in the range of -8.2 to 5.2 kcal/ mol, with low energy parameters and good binding positions. GA could reduce mRNA levels of inflammatory factors IL-6 and TNF-α (p < 0.05), inhibit the expression of CerS6, PKCζ, PPARγ, CD36 (p < 0.05), and enhance the expression of SphK2, Akt, p-Akt/Akt, ISR (p < 0.05). Conclusion: This study investigated the effect and mechanism of GA on reducing ceramide content and reducing IR in mice, and provided an experimental basis for the prevention and treatment of obesity-related diseases.
{"title":"Gooseberry anthocyanins alleviate insulin resistance by regulating ceramide metabolism in high fat diet mice","authors":"XIAN TANG, JUN GAO, JINPENG HUANG, CHENJUAN ZHANG, HONGWEI LIU, JIE WEI","doi":"10.55730/1300-0152.2668","DOIUrl":"https://doi.org/10.55730/1300-0152.2668","url":null,"abstract":"Background/aim: Obesity is the fifth largest risk factor of death in the world. The ceramide produced by obesity is closely related to insulin resistance (IR) caused by obesity. At present, the commercially available weight loss products have large side effects and limited therapeutic effects. Therefore, it is particularly important to find effective natural nontoxic products to treat obesity and explore its possible pathways and mechanisms. Materials and methods: In this paper, a high-fat diet (HFD) mice model was established by intragastric administration of high-fat emulsion to investigate the intervention effect of Gooseberry anthocyanins (GA) on IR in HFD mice. We used molecular docking technology to find the binding sites and binding energy of anthocyanins on CerS6. Real-time PCR was used to detect the effect of GA on the expression of IL-6 and TNF-α mRNA in HFD mice. The expression of S1P/Cer signaling pathway in HFD mice with IR was detected by Western Blot. Results: The results showed that GA could effectively inhibit visceral fat, liver index, the level of TC, TG and the level of LDL-C (p < 0.05), and improved HDL-C, GSH-Px and SOD (p < 0.05). GA decreased the level of insulin sensitivity index from -5.15 to -4.54 and improved insulin sensitivity and IR in HFD mice. The binding energy of anthocyanins on CerS6 was in the range of -8.2 to 5.2 kcal/ mol, with low energy parameters and good binding positions. GA could reduce mRNA levels of inflammatory factors IL-6 and TNF-α (p < 0.05), inhibit the expression of CerS6, PKCζ, PPARγ, CD36 (p < 0.05), and enhance the expression of SphK2, Akt, p-Akt/Akt, ISR (p < 0.05). Conclusion: This study investigated the effect and mechanism of GA on reducing ceramide content and reducing IR in mice, and provided an experimental basis for the prevention and treatment of obesity-related diseases.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Androgen deprivation therapy remains the first-line therapy option for prostate cancer, mostly resulting in the transition of the disease to a castration-resistant state. The lack of androgen signaling during therapy affects various cellular processes, which sometimes paradoxically contributes to cancer progression. As androgen receptor (AR) signaling is known to contribute to oxidative stress regulation, loss of AR may also affect DNA damage level and the response mechanism in oxidant and inflammatory conditions of the prostate tumor microenvironment. Therefore, this study aimed to investigate the role of AR and AR-regulated tumor suppressor NKX3.1 upon oxidative stress-induced DNA damage response (DDR) in the inflammatory tumor microenvironment of the prostate. Materials and methods: Intracellular reactive oxygen species (ROS) level was induced by either inflammatory conditioned media obtained from lipopolysaccharide-induced macrophages or oxidants and measured by dichlorodihydrofluorescein diacetate. In addition to this, DNA damage was subsequently quantified by counting gH2AX foci using an immunofluorescence-based Aklides platform. Altered expression of proteins function in DDR detected by western blotting. Results: Cellular levels of ROS and ROS-induced DNA double-strand break damage were analyzed in the absence and presence of AR signaling upon treatment of prostate cancer cells by either oxidants or inflammatory microenvironment exposure. The results showed that AR suppresses intracellular ROS and contributes to DNA damage recognition under oxidant conditions. Besides, increased DNA damage due to loss of NKX3.1 under inflammatory conditions was alleviated by its overexpression. Moreover, the activation of the DDR mediators caused by AR and NKX3.1 activation in androgen-responsive and castration-resistant prostate cancer cells indicated that the androgen receptor function is essential both in controlling oxidative stress and in activating the ROS-induced DDR. Conclusion: Taken together, it is concluded that the regulatory function of androgen receptor signaling has a vital function in the balance between antioxidant response and DDR activation.
{"title":"Androgen receptor contributes to repairing DNA damage induced by inflammation and oxidative stress in prostate cancer","authors":"BİLGE DEBELEÇ BÜTÜNER, NURŞAH ERTUNÇ HASBAL, ELİF İŞEL, DIRK ROGGENBUCK, KEMAL SAMİ KORKMAZ","doi":"10.55730/1300-0152.2667","DOIUrl":"https://doi.org/10.55730/1300-0152.2667","url":null,"abstract":"Background: Androgen deprivation therapy remains the first-line therapy option for prostate cancer, mostly resulting in the transition of the disease to a castration-resistant state. The lack of androgen signaling during therapy affects various cellular processes, which sometimes paradoxically contributes to cancer progression. As androgen receptor (AR) signaling is known to contribute to oxidative stress regulation, loss of AR may also affect DNA damage level and the response mechanism in oxidant and inflammatory conditions of the prostate tumor microenvironment. Therefore, this study aimed to investigate the role of AR and AR-regulated tumor suppressor NKX3.1 upon oxidative stress-induced DNA damage response (DDR) in the inflammatory tumor microenvironment of the prostate. Materials and methods: Intracellular reactive oxygen species (ROS) level was induced by either inflammatory conditioned media obtained from lipopolysaccharide-induced macrophages or oxidants and measured by dichlorodihydrofluorescein diacetate. In addition to this, DNA damage was subsequently quantified by counting gH2AX foci using an immunofluorescence-based Aklides platform. Altered expression of proteins function in DDR detected by western blotting. Results: Cellular levels of ROS and ROS-induced DNA double-strand break damage were analyzed in the absence and presence of AR signaling upon treatment of prostate cancer cells by either oxidants or inflammatory microenvironment exposure. The results showed that AR suppresses intracellular ROS and contributes to DNA damage recognition under oxidant conditions. Besides, increased DNA damage due to loss of NKX3.1 under inflammatory conditions was alleviated by its overexpression. Moreover, the activation of the DDR mediators caused by AR and NKX3.1 activation in androgen-responsive and castration-resistant prostate cancer cells indicated that the androgen receptor function is essential both in controlling oxidative stress and in activating the ROS-induced DDR. Conclusion: Taken together, it is concluded that the regulatory function of androgen receptor signaling has a vital function in the balance between antioxidant response and DDR activation.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"867 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135943720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A skin wound or perforation triggers a series of homeostatic reactions to safeguard internal organs from invasion by pathogens or other substances that could damage body tissues. An injury may occasionally heal quickly, leading to the closure of the skin's structure. Healing from chronic wounds takes a long time. Although many treatment options are available to manage wound healing, an unmet therapy need remains because of the complexity of the processes and the other factors involved. It is crucial to conduct consistent research on novel therapeutic approaches to find an effective healing agent. Therefore, this work aims to cover various in vitro and in vivo methodologies that could be utilised to examine wound recovery. Before deciding on the optimal course of action, several techniques' benefits, drawbacks, and factors need to be reviewed
{"title":"A review with updated perspectives on in vitro and in vivo wound healing models","authors":"MURNI NAZIRA SARIAN, NABILAH ZULKEFLI, SHAZELI ZAIN, SANDRA MANIAM, SHARIDA FAKURAZI","doi":"10.55730/1300-0152.2659","DOIUrl":"https://doi.org/10.55730/1300-0152.2659","url":null,"abstract":"A skin wound or perforation triggers a series of homeostatic reactions to safeguard internal organs from invasion by pathogens or other substances that could damage body tissues. An injury may occasionally heal quickly, leading to the closure of the skin's structure. Healing from chronic wounds takes a long time. Although many treatment options are available to manage wound healing, an unmet therapy need remains because of the complexity of the processes and the other factors involved. It is crucial to conduct consistent research on novel therapeutic approaches to find an effective healing agent. Therefore, this work aims to cover various in vitro and in vivo methodologies that could be utilised to examine wound recovery. Before deciding on the optimal course of action, several techniques' benefits, drawbacks, and factors need to be reviewed","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135597336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim: The role of PD-L1 in regulating the immunosuppressive tumor microenvironment via its binding on PD-1 receptors is extensively studied. The PD-1/PD-L1 axis is a significant way of cancer immune escape, and PD-L1 expression on tumor cells is suggested as a predictive marker for anti-PD-1/PD-L1 monoclonal antibodies (MoAbs). However, the tumor-intrinsic role of PDL1 is not known well. Therefore, we aimed to investigate the effects of anti-PD-L1 antibodies on the expression of angiogenesis and metastasis-related genes in tumor cells. Materials and methods: The experiments were done with prostate cancer and melanoma cells with low PD-L1 expression (<5%) and prostate and breast cancer cells with high PD-L1 expression (>50%). The gene and protein expressions of VEGFA, E-cadherin, TGFß1, EGFR, and bFGF in tumor cells were assayed at the 3 different doses of the anti-PD-L1 antibody. Results: We found that VEGFA, E-cadherin and TGFß1 expressions increased in PD-L1 high cells but decreased in PD-L1 low cells after anti-PD-L1 treatment. EGFR expression levels were variable in PD-L1 high cells, while decreased in PD-L1 low cells upon treatment. Also, the anti-PD-L1 antibody was found to increase bFGF expression in the prostate cancer cell line with high PD-L1 expression. Conclusion: Our results suggest that the binding of PD-L1 on tumor cells by an anti-PD-L1 monoclonal antibody may affect tumorintrinsic mechanisms. The activation of angiogenesis and metastasis-related pathways by anti-PD-L1 treatment in PD-L1 high tumors might be a tumor-promoting mechanism. The decrease of VEGFA, TGFß1 and EGFR upon anti-PD-L1 treatment in PD-L1 low tumor cells provides a rationale for the use of those antibodies in PD-L1 low tumors.
{"title":"The effects of anti-PD-L1 monoclonal antibody on the expression of angiogenesis and invasion-related genes","authors":"CANSU BABAHAN, SAMIRA ABDI ABGARMI, FATMA GİZEM SONUGÜR, MÜGE ÖÇAL DEMİRTAŞ, HAKAN AKBULUT","doi":"10.55730/1300-0152.2661","DOIUrl":"https://doi.org/10.55730/1300-0152.2661","url":null,"abstract":"Background/aim: The role of PD-L1 in regulating the immunosuppressive tumor microenvironment via its binding on PD-1 receptors is extensively studied. The PD-1/PD-L1 axis is a significant way of cancer immune escape, and PD-L1 expression on tumor cells is suggested as a predictive marker for anti-PD-1/PD-L1 monoclonal antibodies (MoAbs). However, the tumor-intrinsic role of PDL1 is not known well. Therefore, we aimed to investigate the effects of anti-PD-L1 antibodies on the expression of angiogenesis and metastasis-related genes in tumor cells. Materials and methods: The experiments were done with prostate cancer and melanoma cells with low PD-L1 expression (<5%) and prostate and breast cancer cells with high PD-L1 expression (>50%). The gene and protein expressions of VEGFA, E-cadherin, TGFß1, EGFR, and bFGF in tumor cells were assayed at the 3 different doses of the anti-PD-L1 antibody. Results: We found that VEGFA, E-cadherin and TGFß1 expressions increased in PD-L1 high cells but decreased in PD-L1 low cells after anti-PD-L1 treatment. EGFR expression levels were variable in PD-L1 high cells, while decreased in PD-L1 low cells upon treatment. Also, the anti-PD-L1 antibody was found to increase bFGF expression in the prostate cancer cell line with high PD-L1 expression. Conclusion: Our results suggest that the binding of PD-L1 on tumor cells by an anti-PD-L1 monoclonal antibody may affect tumorintrinsic mechanisms. The activation of angiogenesis and metastasis-related pathways by anti-PD-L1 treatment in PD-L1 high tumors might be a tumor-promoting mechanism. The decrease of VEGFA, TGFß1 and EGFR upon anti-PD-L1 treatment in PD-L1 low tumor cells provides a rationale for the use of those antibodies in PD-L1 low tumors.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"83 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135597338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
RUMEYSA ÖZYURT, NİLÜFER ERKASAP, METE ÖZKURT, SERDAR MUSTAFA ERKASAP, KONSTANTİNOS DİMAS, AYŞE ÇAKIR GÜNDOĞDU, ENGİN ULUKAYA
Background/aim: Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and leptin on CRC. Materials and methods: To generate colorectal cancer tumor xenografts, 1 × 107 cells from exponentially growing cultures of HCT15 cells were injected subcutaneously, at the axillary region of the left and right rear flanks of forty NOD.CB17-Prkdcscid/J (NOD/SCID) female mice. The mice were then monitored for the development of tumors and were randomly divided into five groups when tumor sizes reached a volume of approximately 150 mm3 . Mice were used to determine the effectiveness of the gamma-secretase inhibitor (DAPT, Notch inhibitor), the interleukin-1 receptor antagonist (Anakinra) and the leptin receptor antagonist (Allo aca) against tumor growth. The mice were euthanized by CO2 inhalation immediately after the treatments finished, and all efforts were made to minimize suffering. Tumors were excissed for RT-PCR and histological analysis. Results: There is an intact Notch, IL-1, and leptin signaling axis, and in vivo antagonism of Notch, IL-1, and leptin affects mRNA and protein expression of inflammatory and angiogenic molecules. Conclusion: Present data suggest that targeting Notch, IL-1, and leptin may be possesses therapeutic potential in CRC.
{"title":"Targeting of Notch, IL-1, and leptin has therapeutic potential in xenograft colorectal cancer","authors":"RUMEYSA ÖZYURT, NİLÜFER ERKASAP, METE ÖZKURT, SERDAR MUSTAFA ERKASAP, KONSTANTİNOS DİMAS, AYŞE ÇAKIR GÜNDOĞDU, ENGİN ULUKAYA","doi":"10.55730/1300-0152.2663","DOIUrl":"https://doi.org/10.55730/1300-0152.2663","url":null,"abstract":"Background/aim: Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and leptin on CRC. Materials and methods: To generate colorectal cancer tumor xenografts, 1 × 107 cells from exponentially growing cultures of HCT15 cells were injected subcutaneously, at the axillary region of the left and right rear flanks of forty NOD.CB17-Prkdcscid/J (NOD/SCID) female mice. The mice were then monitored for the development of tumors and were randomly divided into five groups when tumor sizes reached a volume of approximately 150 mm3 . Mice were used to determine the effectiveness of the gamma-secretase inhibitor (DAPT, Notch inhibitor), the interleukin-1 receptor antagonist (Anakinra) and the leptin receptor antagonist (Allo aca) against tumor growth. The mice were euthanized by CO2 inhalation immediately after the treatments finished, and all efforts were made to minimize suffering. Tumors were excissed for RT-PCR and histological analysis. Results: There is an intact Notch, IL-1, and leptin signaling axis, and in vivo antagonism of Notch, IL-1, and leptin affects mRNA and protein expression of inflammatory and angiogenic molecules. Conclusion: Present data suggest that targeting Notch, IL-1, and leptin may be possesses therapeutic potential in CRC.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"230 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135597340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ELİF ERTÜRK, OĞUZHAN AKGÜN, YAREN YILDIZ, PINAR KALKAN, OKSANA V. SALOMATINA, NARIMAN F. SALAKHUTDINOV, ENGİN ULUKAYA, FERDA ARI
One of the most prevalent malignancies in women and one of the leading causes of cancer-related death is breast cancer. There is a need for new treatment approaches and drugs for breast cancer. Many studies show the high potential of triterpene compounds and their semisynthetic derivatives as anticancer agents due to their ability to induce apoptosis and suppress tumorigenesis. The effects of soloxolone methyl (SM), a semisynthetic derivative of 18-H-glycyrrhetinic acid, on the cytotoxicity and apoptosis of human breast cancer cell line (T-47D) and cancer stem cell (CSCs) population (mammospheres; CD44+/CD24-antigen) derived from breast cancer cells, were examined in this work. The ATP assay was used to determine SM growth-inhibitory effects. Fluorescent staining, caspase-cleaved cytokeratin 18, and flow cytometry analysis were used to determine the mode of the cell death. In addition, cell death was investigated at protein and gene levels by Western Blotting and PCR, respectively. SM resulted in cytotoxicity in a time and dose dependent manner via ROS production and ER stress in T-47D cells in 2 models. The mode of cell death was apoptosis, evidenced by phosphatidylserine exposure, caspase activation, and bax overexpression. In mammospheres as 3D model, SM decreased stem cell properties and induced cell death. Taken together, SM may be a promising agent in the treatment of breast cancer, especially due to its antigrowth activity on CSCs.
乳腺癌是妇女中最常见的恶性肿瘤之一，也是癌症相关死亡的主要原因之一。乳腺癌需要新的治疗方法和药物。许多研究表明，由于三萜化合物及其半合成衍生物具有诱导细胞凋亡和抑制肿瘤发生的能力，它们作为抗癌药物具有很高的潜力。18- h -甘草次酸半合成衍生物甲基索罗洛酮(SM)对人乳腺癌细胞系(T-47D)和癌症干细胞(CSCs)群体(乳腺微球;CD44+/ cd24抗原)来源于乳腺癌细胞。ATP法测定SM的生长抑制作用。采用荧光染色、caspase-cleaved细胞角蛋白18和流式细胞术分析确定细胞死亡方式。此外，用Western Blotting和PCR分别在蛋白和基因水平上研究细胞死亡。SM通过产生ROS和内质网应激对2种模型的T-47D细胞产生时间和剂量依赖性的细胞毒性。磷脂酰丝氨酸暴露、caspase激活和bax过表达证明细胞死亡方式为凋亡。在乳腺球体作为3D模型中，SM降低了干细胞特性并诱导细胞死亡。综上所述，SM可能是一种很有前景的治疗乳腺癌的药物，特别是由于其对csc的抗生长活性。
{"title":"Soloxolone methyl induces apoptosis and oxidative/ER stress in breast cancer cells and target cancer stem cell population","authors":"ELİF ERTÜRK, OĞUZHAN AKGÜN, YAREN YILDIZ, PINAR KALKAN, OKSANA V. SALOMATINA, NARIMAN F. SALAKHUTDINOV, ENGİN ULUKAYA, FERDA ARI","doi":"10.55730/1300-0152.2660","DOIUrl":"https://doi.org/10.55730/1300-0152.2660","url":null,"abstract":"One of the most prevalent malignancies in women and one of the leading causes of cancer-related death is breast cancer. There is a need for new treatment approaches and drugs for breast cancer. Many studies show the high potential of triterpene compounds and their semisynthetic derivatives as anticancer agents due to their ability to induce apoptosis and suppress tumorigenesis. The effects of soloxolone methyl (SM), a semisynthetic derivative of 18-H-glycyrrhetinic acid, on the cytotoxicity and apoptosis of human breast cancer cell line (T-47D) and cancer stem cell (CSCs) population (mammospheres; CD44+/CD24-antigen) derived from breast cancer cells, were examined in this work. The ATP assay was used to determine SM growth-inhibitory effects. Fluorescent staining, caspase-cleaved cytokeratin 18, and flow cytometry analysis were used to determine the mode of the cell death. In addition, cell death was investigated at protein and gene levels by Western Blotting and PCR, respectively. SM resulted in cytotoxicity in a time and dose dependent manner via ROS production and ER stress in T-47D cells in 2 models. The mode of cell death was apoptosis, evidenced by phosphatidylserine exposure, caspase activation, and bax overexpression. In mammospheres as 3D model, SM decreased stem cell properties and induced cell death. Taken together, SM may be a promising agent in the treatment of breast cancer, especially due to its antigrowth activity on CSCs.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135597335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DAVID GONZALEZ FLORES, JAVIER ESPINO, JOSE A. PARIENTE
Background/aim: The novel field of nanomaterials allows infinite possibilities in order to create antioxidant therapies. The present review is aimed to describe the state of art concerning on nanomaterials and their effects on reactive oxygen species (ROS) production. A wide range of nanoparticles has been designed for this purpose, and each one possesses some particular characteristics which allow these significant antioxidant results. Several in vivo and in vitro works state the ability of these nanoparticles to mimic the redox systems of the cells, and thus, the potential role of nanoparticles as antioxidant treatment for several diseases. Materials and methods: This paper was written after a review of the articles published on the field, using the "PubMed" and "Research Gate" databases. Results: The main types of nanoparticles are listed and explained below, offering a global vision of the field with great interest for research. Antitumor chemo- and radiotherapies have been found to improve efficacy by enhancing the selectivity of cytocidal effects and minimizing systemic adverse effects when such materials are used. Furthermore, catalytic nanomaterials can execute energy-free antioxidant cycles that scavenge the most harmful reactive oxygen species via SOD- and catalase-like activities. Conclusion: This unique method is projected to result in significant gains in the long run. However, due to a lack of understanding of potential adverse body reactions to these novel strategies, caution must be exercised. Analyzing the biocompatibility of these nanomaterials carefully, particularly in terms of biokinetics and the problems that could arise from long-term retention of nonbiodegradable inorganic nanomaterials, is required.
{"title":"Antioxidant potential of nanomaterials","authors":"DAVID GONZALEZ FLORES, JAVIER ESPINO, JOSE A. PARIENTE","doi":"10.55730/1300-0152.2658","DOIUrl":"https://doi.org/10.55730/1300-0152.2658","url":null,"abstract":"Background/aim: The novel field of nanomaterials allows infinite possibilities in order to create antioxidant therapies. The present review is aimed to describe the state of art concerning on nanomaterials and their effects on reactive oxygen species (ROS) production. A wide range of nanoparticles has been designed for this purpose, and each one possesses some particular characteristics which allow these significant antioxidant results. Several in vivo and in vitro works state the ability of these nanoparticles to mimic the redox systems of the cells, and thus, the potential role of nanoparticles as antioxidant treatment for several diseases. Materials and methods: This paper was written after a review of the articles published on the field, using the \"PubMed\" and \"Research Gate\" databases. Results: The main types of nanoparticles are listed and explained below, offering a global vision of the field with great interest for research. Antitumor chemo- and radiotherapies have been found to improve efficacy by enhancing the selectivity of cytocidal effects and minimizing systemic adverse effects when such materials are used. Furthermore, catalytic nanomaterials can execute energy-free antioxidant cycles that scavenge the most harmful reactive oxygen species via SOD- and catalase-like activities. Conclusion: This unique method is projected to result in significant gains in the long run. However, due to a lack of understanding of potential adverse body reactions to these novel strategies, caution must be exercised. Analyzing the biocompatibility of these nanomaterials carefully, particularly in terms of biokinetics and the problems that could arise from long-term retention of nonbiodegradable inorganic nanomaterials, is required.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"70 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135597337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background/aim Photodynamic therapy (PDT) has received great attention over the past decade in the treatment of diseases such as leukemia which is a cancer of the blood and bone marrow cells that causes a significant number of deaths worldwide. In this study, it was aimed to investigate the effects of Nile blue-mediated PDT (NB-mediated PDT) on HL60 cells. Materials and methods The effect of NB-mediated PDT on cell proliferation was evaluated with cell volume analysis using flow cytometry at 24 h. Cell apoptosis, ROS production, mitochondrial membrane potential, and cell cycle analysis were evaluated using annexin V-FITC, H2DCFDA, JC-1, and PI staining, respectively, by flow cytometry and fluorescence microscopy. The morphological and ultrastructural analyses were examined by Giemsa staining and SEM. CD11b staining is used to determine the differentiation of leukemia cells. Results NB-mediated PDT induced an apoptotic response at 12.5 μM in HL60 cells. When Giemsa staining and SEM images were evaluated, apoptotic bodies, holes, and occasional folds were detected on the surfaces of cells in the NB-mediated PDT group. Conclusion The NB-mediated PDT had no effect on the differentiation of leukemia cells, but this therapy affects the growth of HL60 cells in vitro, which may provide a new idea for removing leukemic cells from bone marrow intended for autologous transplant.
{"title":"Antileukemic potential of Nile blue-mediated photodynamic therapy on HL60 human myeloid leukemia cells","authors":"SERÇİN ÖZLEM ÇALIŞKAN, AYNUR KARADAĞ, BARIŞ UZUNOK, NUMAN TAŞPINAR, BERNA AKIN, METİN ÇALIŞKAN, RAHŞAN ILIKÇI SAĞKAN","doi":"10.55730/1300-0152.2662","DOIUrl":"https://doi.org/10.55730/1300-0152.2662","url":null,"abstract":"Background/aim Photodynamic therapy (PDT) has received great attention over the past decade in the treatment of diseases such as leukemia which is a cancer of the blood and bone marrow cells that causes a significant number of deaths worldwide. In this study, it was aimed to investigate the effects of Nile blue-mediated PDT (NB-mediated PDT) on HL60 cells. Materials and methods The effect of NB-mediated PDT on cell proliferation was evaluated with cell volume analysis using flow cytometry at 24 h. Cell apoptosis, ROS production, mitochondrial membrane potential, and cell cycle analysis were evaluated using annexin V-FITC, H2DCFDA, JC-1, and PI staining, respectively, by flow cytometry and fluorescence microscopy. The morphological and ultrastructural analyses were examined by Giemsa staining and SEM. CD11b staining is used to determine the differentiation of leukemia cells. Results NB-mediated PDT induced an apoptotic response at 12.5 μM in HL60 cells. When Giemsa staining and SEM images were evaluated, apoptotic bodies, holes, and occasional folds were detected on the surfaces of cells in the NB-mediated PDT group. Conclusion The NB-mediated PDT had no effect on the differentiation of leukemia cells, but this therapy affects the growth of HL60 cells in vitro, which may provide a new idea for removing leukemic cells from bone marrow intended for autologous transplant.","PeriodicalId":23358,"journal":{"name":"Turkish Journal of Biology","volume":"208 1","pages":"276 - 289"},"PeriodicalIF":0.0,"publicationDate":"2023-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135597339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：