Anti-cancer agents in medicinal chemistry最新文献

Introduction: Copper complexes, as endogenous metals, have potential in cancer therapy, addressing issues associated with cisplatin. Since cisplatin uses Copper Transporter 1 (CTR1) for cellular entry, copper complexes may utilize this pathway to enhance transport efficiency.

Methods: The Cu/Na dipicolinic acid complex was synthesized to assess its cytotoxicity, induction of apoptosis, drug resistance, and inflammation in cancerous and normal lung cells. The effects of oxidative stress on erythrocytes were also examined.

Results: Cytotoxicity tests (MTT and SRB) showed superior inhibitory effects on A549 lung cancer cells compared to cisplatin, with no toxicity observed in MRC-5 normal lung fibroblast cells. Real-time PCR revealed increased caspase-3 expression (extrinsic apoptosis) for the complex compared to cisplatin, possibly due to CTR1- mediated entry. The complex did not induce drug resistance, as shown by AKT1 expression, and reduced TNF-α expression, preventing inflammation in normal cells. In contrast to cisplatin, the complex caused minimal oxidative stress in erythrocytes.

Discussion: It can be concluded that the Cu/Na dipicolinic acid complex may be easily transported by CTR1 to malignant tumors, particularly lung cancer. This complex has the ability to inhibit cancer cell growth and induce apoptosis in lung cancer cells. Therefore, copper complexes show promise as potential therapeutic options for treating this type of cancer.

Conclusion: The copper/sodium complex demonstrates enhanced therapeutic efficacy in lung cancer cells, requiring lower doses than cisplatin, while being safer for normal cells and erythrocytes.

Introduction: The presence of severe hypoxic stress can drive tumor growth, angiogenesis, and metastatic characteristics via up-regulated hypoxia-inducible factor 1-alpha (HIF-1α). Hence, targeting HIF-1α is considered a promising strategy, as increased HIF-1α activity is a key factor in the aggressive phenotype of malignancies. In this study, we aimed to investigate the anti-cancer effects of several flavonoids, both single and in combination with PX-478, in breast cancer cell lines.

Methods: We tested the effects of luteolin and PX-478, both alone and in combination, on HIF-1α level in breast cancer cells under hypoxia using the cell viability assay. To determine the rationale for the cell growth inhibition induced by the luteolin+PX-478 combination, we conducted experiments to assess cell survival, apoptosis, cell cycle, invasion, and migration under both normoxic and hypoxic conditions. Furthermore, we evaluated the effect of this combination on DNA damage response under hypoxic stress via Comet assay and immunofluorescence staining.

Results: Our findings revealed that the luteolin+PX-478 combination significantly suppressed the growth of MDA-MB-231 cells. In addition, we assessed time-dependent expression of HIF1α in MDA-MB-231 cells and observed that the combination of luteolin and PX-478 down-regulated the HIF-1α level. Finally, we found that the luteolin+PX-478 combination induced apoptosis and G2 cell cycle arrest and enhanced DNA damage response. This combination also sensitized breast cancer cells to ionizing radiation in hypoxic stress.

Discussion: The findings suggested that targeting HIF-1α with a combination of luteolin and PX-478 may provide a synergistic approach to suppressing tumor growth and enhancing therapeutic response under hypoxic conditions. The observed effects on apoptosis, cell cycle arrest, and DNA damage response indicated that this combination could be a promising strategy for overcoming hypoxia-induced resistance in breast cancer therapy.

Conclusion: Collectively, our results suggested the combination of luteolin and PX-478 to enhance the anticancer effects of PX-478 in breast carcinoma cells by impeding the cell growth and inducing DNA damage response under hypoxia.

Cancer remains a growing challenge in modern society, presenting a significant obstacle in both developed and developing countries. Conventional treatments are often costly and limited by issues such as drug resistance and undesirable side effects. Consequently, the exploration of natural compounds has emerged as a promising strategy for developing more effective and tolerable cancer therapies. Among these, Ferula plants have gained attention for their potential anticancer components. Notably, two coumarin compounds derived from these plants, farnesiferol C and umbelliferone, have demonstrated substantial anticancer activity, as supported by an increasing number of published studies. This review aims to consolidate existing evidence on the anticancer effects of farnesiferol C and umbelliferone while comparing their efficacy as potential therapeutic agents. To accomplish this, a comprehensive literature search was conducted using the terms "umbelliferone" and "farnesiferol C" paired with "anticancer" across databases such as ISI Web of Knowledge, PubMed, and Google Scholar. Relevant studies up to March 2024 were retrieved, summarized, and incorporated into this analysis. The findings indicate that both compounds exhibit significant anticancer properties, positioning them as viable candidates for future drug development. A comparative analysis of their IC50 values, the concentration required to inhibit 50% of cancer cell growth, reveals that farnesiferol C demonstrates greater cytotoxic potency against various cancer cell lines compared to umbelliferone. However, while these results are encouraging, further research is recommended, particularly in vivo studies to evaluate the compounds' toxicity and therapeutic potential in living organisms.

Background: Lung cancer remains a leading cause of cancer-related deaths worldwide, with its incidence continuing to rise. Despite advancements in clinical treatments, their effectiveness is often restricted, emphasizing the need for novel therapeutic strategies. Natural products have long been explored for drug development, and among them, polysaccharides have gained significant attention due to their biocompatibility, biodegradability, and multiple biological functions.

Methods: A comprehensive review examined contemporary research on the anticancer properties of natural polysaccharides, focusing specifically on their effects in lung cancer. The analysis included studies investigating their influence on cancer cell growth, immune system modulation, and therapeutic outcomes. Evidence from laboratory (in vitro), animal (in vivo), and clinical studies was evaluated to provide a comprehensive overview of their potential role in lung cancer management.

Results: Findings from recent studies indicate that polysaccharides can effectively inhibit the proliferation of lung cancer cells, thereby slowing tumor development. These compounds also appear to enhance immune responses by activating various immune cells and regulating cytokine production. Furthermore, polysaccharides have been shown to positively affect the gut microbiota, which may contribute to improved drug efficacy and a reduction in resistance to chemotherapy.

Discussion: The evidence suggests that natural polysaccharides exert multifaceted effects in the context of lung cancer treatment. Their ability to directly suppress tumor growth, modulate the immune system, and interact with the gut microbiome positions them as promising adjuncts to existing therapies. However, the precise molecular mechanisms underlying these effects are not yet fully understood, and variability in study designs warrants cautious interpretation of the results.

Conclusion: Natural polysaccharides represent a promising complementary approach for lung cancer therapy, given their potential to inhibit tumor progression, enhance immune function, and improve the effectiveness of conventional drugs. Continued research is essential to fully elucidate their mechanisms of action and to translate these findings into effective clinical interventions.

Introduction: Microbial metabolites represent a valuable source of bioactive compounds with promising anticancer properties. However, conventional drug discovery approaches are time-intensive and resource-demanding.

Methods: Recent developments in artificial intelligence (AI), machine learning (ML), molecular docking, and quantitative structure-activity relationship (QSAR) modeling have been examined for their role in the identification and optimization of microbial metabolites.

Results: AI-driven approaches have significantly enhanced compound screening and prediction of therapeutic efficacy. Nanocarrier-based drug delivery systems have improved the bioavailability, specificity, and stability of microbial metabolites while minimizing systemic toxicity. Despite these advancements, challenges remain in clinical translation due to the lack of in vivo validation and comprehensive pharmacokinetic data.

Discussion: This review highlights the integration of advanced computational tools and nanotechnology in accelerating the discovery and delivery of microbial-derived anticancer agents.

Conclusion: Future directions should focus on integrating AI with synthetic biology to engineer microbial strains capable of producing enhanced bioactive compounds. Additionally, leveraging nanotechnology could refine targeted delivery mechanisms. A deeper understanding of molecular pathways and drug resistance mechanisms is essential to support the development of combination therapies. Overall, microbialderived compounds hold substantial potential in advancing precision oncology.

Introduction: VPS9 domain-containing 1 antisense RNA 1 (VPS9D1-AS1), also known as c-Mycupregulated lncRNA (MYU) and FAK-interacting and stabilizing lncRNA (FAISL), is a novel long non-coding RNA (lncRNA) located at the human chromosome 16q24.3 locus. It has been reported to be highly expressed in various human cancers and associated with poor clinical pathological features and unfavorable prognosis in eight of the malignant tumors.

Methods: A comprehensive literature search was conducted using PubMed, Web of Science, and Google Scholar databases to identify relevant articles on "VPS9D1-AS1", "MYU", or "FAISL". Only peer-reviewed publications were included, and articles related to oncology were specifically collected.

Results: Mechanistically, VPS9D1-AS1 serves as a key regulator in four molecular models: signal, scaffold, guide, and decoy. These functions allow it to regulate the expression of target genes and activation of signaling pathways, thereby influencing the malignant phenotype of tumors.

Discussion: The diverse molecular mechanisms of VPS9D1-AS1 highlight its significant role in the development and progression of various cancers. Its ability to act as a signal, scaffold, guide, and decoy suggests that it can influence multiple aspects of tumor biology, including proliferation, invasion, and metastasis.

Conclusion: VPS9D1-AS1 plays a significant role in the development and progression of various cancers through its diverse molecular mechanisms. Further research on VPS9D1-AS1 may provide valuable insights, which may facilitate the development of new diagnostic and therapeutic strategies for cancer.

Background: Hepatocellular carcinoma (HCC) ranks among the leading causes of cancer-related deaths on a global scale. This study aimed to evaluate the effects of euxanthone on the proliferation of HCC cell lines and elucidate the underlying molecular mechanisms.

Methods: HCC cell lines (HepG2, Huh-7, SNU-398, SK-HEP-1, Hep3B) and the normal liver cell line THLE-2 were cultured and treated with euxanthone at concentrations between 0 and 100 μM. Cell viability was evaluated using the MTT assay, while phase contrast microscopy and cell cycle analysis were performed to evaluate morphological changes and cell cycle distribution. qRT-PCR was utilized to measure miRNA and mRNA expression levels, while a dual luciferase reporter assay validated the interaction between miR-199a-5p and E2F3.

Results: Euxanthone significantly (P < 0.05) inhibited cell proliferation in all HCC cell lines, with IC₂⁽ values between 6.25 and 25 μM. HepG2 cells exhibited pronounced sensitivity, with an IC₂⁽ of 6.25 μM. Euxanthone induced a G1 phase arrest, characterized by decreased expression of Cyclin D1 and E, and increased levels of p21. Additionally, it upregulated miR-199a-5p, which was identified as a mediator of the antiproliferative effects by targeting E2F3. Euxanthone treatment also significantly (P < 0.05) inhibited HepG2 cell migration in a wound healing assay.

Conclusion: Taken together, euxanthone exerts antiproliferative effects on HCC cells via the miR-199a-5p-E2F3 axis and inhibits cell migration. These findings support its potential as a therapeutic agent for HCC, highlighting the need for further investigation into its clinical applications.

Introduction: Chemotherapy faces limitations such as toxicity and resistance, necessitating novel cancer treatments. Green-synthesized zinc oxide nanoparticles (ZnO-NPs) have attracted attention for their safety, biocompatibility, and therapeutic potential. This study investigates the anticancer efficacy of ZnO-NPs synthesized using the extracellular matrix of Aspergillus biplanus against colorectal cancer cell lines (HCT-116).

Methods: ZnO-NPs were synthesized extracellularly using A. biplanus fungal extract. The nanoparticles were characterized through UV-Vis spectrophotometry, showing an absorbance peak at 375 nm, and scanning electron microscopy (SEM), which determined their morphology and size. The anticancer activity was evaluated in vitro using HCT-116 cells. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were assessed to understand the mechanism of cytotoxicity. In vivo studies were proposed for further validation.

Results: The synthesized ZnO-NPs appeared pale white and exhibited a characteristic absorbance at 375 nm. SEM revealed spherical particles ranging from 35-150 nm. The ZnO-NPs showed strong anticancer activity with an IC50 value of 40.6 μg/mL. ROS levels increased significantly in treated cells, while the MMP decreased to 77.25% compared to 100% in controls.

Discussion: ZnO-NPs exerted cytotoxic effects via ROS generation and mitochondrial dysfunction. These results underscore the nanoparticles' ability to induce apoptosis in cancer cells through oxidative stress pathways.

Conclusion: Biogenically synthesized ZnO-NPs from A. biplanus show promise as eco-friendly anticancer agents. Further in vivo studies are recommended to confirm their therapeutic potential.

Introduction: Ursolic acid (UA) exhibits antitumor activity; however, its effects and mechanisms on triple-negative breast cancer (TNBC) cells are not well understood. The present study aimed to explore the anti- TNBC mechanisms of UA by network pharmacology and experimental validation.

Methods: TNBC cell lines MDA-MB-231 and BT-549 cells were treated with UA. A CCK-8 assay was performed to detect cell growth, while flow cytometry assessed cell cycle arrest and apoptosis. The underlying mechanism and potential targets of UA for TNBC treatment were investigated by network pharmacology, including PharmMapper database, GO, KEGG enrichment, and PPI analysis. The protein expressions and phosphorylation levels of FGFR1, AKT, and ERK were measured by western blot. Pull-down assay, cellular thermal shift assay (CETSA), and molecular docking were used to analyze the interaction between UA and FGFR1. Xenograft models were established to examine the effect of UA on TNBC tumor growth.

Results: UA effectively reduced cell viability, induced apoptosis, and arrested cell cycle in TNBC cells. Moreover, UA significantly regulated the expression of Bcl-2 and Bax to induce apoptosis. The results of network pharmacology and western blot suggested that UA reduced FGFR1/AKT/ERK pathway. Furthermore, pull-down, CETSA, and molecular docking results revealed that UA directly bound to FGFR1. In the xenograft model, UA inhibited the growth by suppressing FGFR1.

Discussion: In this study, we employed network pharmacology and experimental approaches to elucidate the mechanism of UA on TNBC. The results demonstrated that UA targeted FGFR1 to inhibit TNBC via mediating FGFR1/AKT/ERK pathway.

Conclusions: Our findings demonstrate that UA inhibits the FGFR1/AKT/ERK pathway by directly targeting FGFR1, thereby suppressing TNBC progression and supporting its potential as a therapeutic agent for TNBC treatment.

Ovarian cancer remains a significant public health challenge. It originates in the ovaries and presents in various histological subtypes. Surgery and chemotherapy are the most suitable treatments to combat this disease. This study aims to provide insights into the mechanisms and biological complexity needed to understand the pathogenesis of recurrent ovarian cancer. A thorough review of the relevant literature on recurrent ovarian cancer and immunotherapy was conducted to gather information on genetic factors, immune responses, therapeutic strategies, and other pertinent data. The findings were analyzed and discussed to provide an in-depth understanding aligned with the study's objectives. Recurrent ovarian cancer is a major clinical challenge that occurs when the disease returns after initial treatment and a period of remission. Recurrence typically arises when residual cancer cells remain in the body after treatment, eventually leading to disease progression. Genetic factors, including mutations in BRCA1/BRCA2 and other genetic markers, play a crucial role in ovarian cancer recurrence and influence responses to therapies. The immune system's response to cancer cells is also critical, with therapeutic interventions either enhancing or reducing efficacy. The complex mechanisms underlying ovarian cancer and its recurrence have left many aspects of the disease pathway still to be fully understood. In conclusion, a comprehensive understanding of genetic and immune factors is crucial for developing effective and personalized treatments.