Weichong Zhao, Lihui Wang, Hua Chen, L. Qi, Ru-hui Yang, Lei Ning
Background: Prostate cancer is common in men worldwide and its incidence in China has increased over the last 2 decades. The present study assessed the cytotoxicity of jatrorrhizine-platinum(II) complex [JR-P(II)] against prostate cancer and investigated the associated mechanism. Material/Methods: MTT assay was used to assess the anti-proliferative potential and flow cytometry was used to assess apoptosis induction ability of JR-P(II). The protein expression was determined using Western blot assay. JR-P(II)induced changes in Akt mRNA were assessed by RT-PCR assay and MMP was evaluated by flow cytometry using Rhodamine 123 staining. Results: JR-P(II) inhibited 22Rv1 cell and LNCaP cell viability by 17% and 24%, respectively, after treatment with 16 μM JR-P(II). In JR-P(II)-treated 22Rv1 cells and LNCaP cells, the levels of cleaved-PARP and caspase-3 were elevated by 4.0, 8.0, and 16 μM JR-P(II). JR-P(II) treatment increased 22Rv1 and LNCaP cell populations in S phase, with reduction of G1/G0 and G2/M phase cell count. Treatment of 22Rv1 and LNCaP cells with JR-P(II) caused reduction of cyclin E1/A1/D1, pRb, and E2F1 proteins. Moreover, JR-P(II) treatment elevated p53 expression in 22Rv1 and LNCaP cells. JR-P(II) treatment raised ROS level and suppressed MMP in 22Rv1 and LNCaP cells. JRP(II) treatment increased cytochrome c and Bax expression, and reduced Bcl-2 expression in 22Rv1 and LNCaP cells. In JR-P(II)-treated 22Rv1 and LNCaP cells, PI3K/Akt/ERK activation was downregulated relative to the control group. JAK2 and STAT3 phosphorylation gradually decreased with increased JR-P(II) concentration, from 4.0 to 16 μM. Conclusions: JR-P(II) inhibits prostate cancer cell proliferative potential via oxidative damage-induced apoptosis, and it downregulated PI3K/AKT and STA3/JAK2 pathway activation in prostate cancer cells. Therefore, JR-P(II) shows promise for use in treatment of prostate cancer.
{"title":"Inhibitory Effect of Jatrorrhizine-Platinum(II) Complex on Prostate Cancer Cells via PI3K/AKT and STA3/JAK2 Phosphorylation Downregulation","authors":"Weichong Zhao, Lihui Wang, Hua Chen, L. Qi, Ru-hui Yang, Lei Ning","doi":"10.12659/MSM.924542","DOIUrl":"https://doi.org/10.12659/MSM.924542","url":null,"abstract":"Background: Prostate cancer is common in men worldwide and its incidence in China has increased over the last 2 decades. The present study assessed the cytotoxicity of jatrorrhizine-platinum(II) complex [JR-P(II)] against prostate cancer and investigated the associated mechanism. Material/Methods: MTT assay was used to assess the anti-proliferative potential and flow cytometry was used to assess apoptosis induction ability of JR-P(II). The protein expression was determined using Western blot assay. JR-P(II)induced changes in Akt mRNA were assessed by RT-PCR assay and MMP was evaluated by flow cytometry using Rhodamine 123 staining. Results: JR-P(II) inhibited 22Rv1 cell and LNCaP cell viability by 17% and 24%, respectively, after treatment with 16 μM JR-P(II). In JR-P(II)-treated 22Rv1 cells and LNCaP cells, the levels of cleaved-PARP and caspase-3 were elevated by 4.0, 8.0, and 16 μM JR-P(II). JR-P(II) treatment increased 22Rv1 and LNCaP cell populations in S phase, with reduction of G1/G0 and G2/M phase cell count. Treatment of 22Rv1 and LNCaP cells with JR-P(II) caused reduction of cyclin E1/A1/D1, pRb, and E2F1 proteins. Moreover, JR-P(II) treatment elevated p53 expression in 22Rv1 and LNCaP cells. JR-P(II) treatment raised ROS level and suppressed MMP in 22Rv1 and LNCaP cells. JRP(II) treatment increased cytochrome c and Bax expression, and reduced Bcl-2 expression in 22Rv1 and LNCaP cells. In JR-P(II)-treated 22Rv1 and LNCaP cells, PI3K/Akt/ERK activation was downregulated relative to the control group. JAK2 and STAT3 phosphorylation gradually decreased with increased JR-P(II) concentration, from 4.0 to 16 μM. Conclusions: JR-P(II) inhibits prostate cancer cell proliferative potential via oxidative damage-induced apoptosis, and it downregulated PI3K/AKT and STA3/JAK2 pathway activation in prostate cancer cells. Therefore, JR-P(II) shows promise for use in treatment of prostate cancer.","PeriodicalId":49834,"journal":{"name":"Medical Science Monitor","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2020-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48857929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The currently used anticancer drugs against breast cancer possess serious side effects, have limited efficacy, and often lead to recurrence of the malignancy. The main aim of the current research was to investigate the anticancer potential of girinimbine, a naturally occurring carbazole alkaloid, against estrogen receptor (ER)negative breast cancer cells (MDA-MB-453) along with its effects on cell migration and invasion, apoptosis, and the MEK/ERK/STAT3 pathway. Material/Methods: MTT assay was used to evaluate antiproliferative effects of girinimbine while as clonogenic assay was used to study cell colony formation. Transwell migration and invasion assays were performed to study the effects on cell migration and invasion. Fluorescence microscopy using acridine orange/ethidium bromide was used to study apoptotic effects of girinimbine, which was quantified by annexin V-FITC assay. Effects of girinimbine on the MEK/ERK and STAT3 signaling pathways were evaluated by western blot assay. Results: Results showed that girinimbine exhibited dose-dependent as well as time-dependent antiproliferative effects in MDA-MB-453 cells; in addition it strongly inhibited cell colony potency of these cancerous cells. Girinimbine could inhibit both cancer cell migration as well as invasion. Girinimbine induced potent chromatin condensation and nuclear fragmentation. The percentage of both early and late apoptotic cells increased significantly after girinimbine exposure. The anticancer effects of girinimbine were shown to be mediated via inhibition of the MEK/ERK as well as the STAT3 signaling pathways. Conclusions: In conclusion, it may be proposed that girinimbine could be a promising anticancer agent against breast cancer provided further in-depth studies are carried out.
{"title":"Girinimbine Inhibits the Proliferation, Migration, and Invasion of Human Breast Cancer Cells via Induction of Apoptosis, Suppression of Cell Migration and Invasion and Inhibition of MEK/ERK and STAT3 Signaling Pathways","authors":"Lihong Yang, Xuehui Yu","doi":"10.12659/msm.921477","DOIUrl":"https://doi.org/10.12659/msm.921477","url":null,"abstract":"Background: The currently used anticancer drugs against breast cancer possess serious side effects, have limited efficacy, and often lead to recurrence of the malignancy. The main aim of the current research was to investigate the anticancer potential of girinimbine, a naturally occurring carbazole alkaloid, against estrogen receptor (ER)negative breast cancer cells (MDA-MB-453) along with its effects on cell migration and invasion, apoptosis, and the MEK/ERK/STAT3 pathway. Material/Methods: MTT assay was used to evaluate antiproliferative effects of girinimbine while as clonogenic assay was used to study cell colony formation. Transwell migration and invasion assays were performed to study the effects on cell migration and invasion. Fluorescence microscopy using acridine orange/ethidium bromide was used to study apoptotic effects of girinimbine, which was quantified by annexin V-FITC assay. Effects of girinimbine on the MEK/ERK and STAT3 signaling pathways were evaluated by western blot assay. Results: Results showed that girinimbine exhibited dose-dependent as well as time-dependent antiproliferative effects in MDA-MB-453 cells; in addition it strongly inhibited cell colony potency of these cancerous cells. Girinimbine could inhibit both cancer cell migration as well as invasion. Girinimbine induced potent chromatin condensation and nuclear fragmentation. The percentage of both early and late apoptotic cells increased significantly after girinimbine exposure. The anticancer effects of girinimbine were shown to be mediated via inhibition of the MEK/ERK as well as the STAT3 signaling pathways. Conclusions: In conclusion, it may be proposed that girinimbine could be a promising anticancer agent against breast cancer provided further in-depth studies are carried out.","PeriodicalId":49834,"journal":{"name":"Medical Science Monitor","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2020-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42804457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of Cancer Cell Growth by Abietic Acid in Cisplatin-Resistant Human Nasopharyngeal Cancer Cells Is Mediated via G2/M Cell Cycle Arrest, Blocking the PI3K/AKT/mTOR Signalling Pathway, and Suppression of Cell Migration and Invasion","authors":"Haojie Wen, Qiao Mo, Yi Cui, Jinyongg Tangg","doi":"10.12659/MSM.914982","DOIUrl":"https://doi.org/10.12659/MSM.914982","url":null,"abstract":"","PeriodicalId":49834,"journal":{"name":"Medical Science Monitor","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2019-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47989629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carmen E. Gonzalez, M. T. Cruz-Carreras, N. Guha-Thakurta, Ninotchka Brydges, Patrick S Chaftari
{"title":"A Rare Case of Extramedullary Plasmacytoma of the Pleura Causing Spinal Cord Compression in a Patient with Multiple Myeloma","authors":"Carmen E. Gonzalez, M. T. Cruz-Carreras, N. Guha-Thakurta, Ninotchka Brydges, Patrick S Chaftari","doi":"10.12659/MSCR.901989","DOIUrl":"https://doi.org/10.12659/MSCR.901989","url":null,"abstract":"","PeriodicalId":49834,"journal":{"name":"Medical Science Monitor","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2017-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44469246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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