Résumé
The rapidly developing resistance of cancers to chemotherapy agents and the severe cytotoxicity of such agents to normal cells are major stumbling blocks in current cancer treatments. Most current chemotherapy agents have significant cytotoxicity, which leads to devastating adverse effects and results in a substandard quality of life, including increased daily morbidity and premature mortality. The death receptor of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can sidestep p53-dependent pathways to induce tumor cell apoptosis without damaging most normal cells. However, various cancer cells can develop resistance to TRAIL-induced apoptosis via different pathways. Therefore, it is critical to find an efficient TRAIL sensitizer to reverse the resistance of tumor cells to TRAIL, and to reinforce TRAIL's ability to induce tumor cell apoptosis. In recent years, traditional Chinese medicines and their active ingredients have shown great potential to trigger apoptotic cell death in TRAIL-resistant cancer cell lines. This review aims to collate information about Chinese medicines that can effectively reverse the resistance of tumor cells to TRAIL and enhance TRAIL's ability to induce apoptosis. We explore the therapeutic potential of TRAIL and provide new ideas for the development of TRAIL therapy and the generation of new anti-cancer drugs for human cancer treatment. This study involved an extensive review of studies obtained from literature searches of electronic databases such as Google Scholar and PubMed. "TRAIL sensitize" and "Chinese medicine" were the search keywords. We then isolated newly published studies on the mechanisms of TRAIL-induced apoptosis. The name of each plant was validated using certified databases such as The Plant List. This study indicates that TRAIL can be combined with different Chinese medicine components through intrinsic or extrinsic pathways to promote cancer cell apoptosis. It also demonstrates that the active ingredients of traditional Chinese medicines enhance the sensitivity of cancer cells to TRAIL-mediated apoptosis. This provides useful information regarding traditional Chinese medicine treatment, the development of TRAIL-based therapies, and the treatment of cancer.
Résumé
Objective: To explore the possibility of promoting tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis in prostate cancer PC-3 cell by inhibiting Krüppel-like factor 5 (KLF5). Methods: MTT assay, flow cytometry, Western blot assay and qRT-PCR assay were deployed to detect the cell viability, apoptosis and apoptotic markers in KLF5-inhibited and TRAIL-induced PC-3 cells. Results: After KLF5 was inhibited in TRAIL-induced PC-3 cells, cell viability reduced, apoptosis enhanced, the expressions of DR4 and DR5 increased while the expression of cellular fas-associated death domain-like interleukin-1β converting enzyme inhibitory protein (c-FLIP) decreased. Conclusion: Inhibiting KLF5 suppresses cell viability by promoting TRAIL-induced apoptosis in prostate cancer cell PC-3. It may be a potential means to treat hormone-insensitive prostate cancer.
Résumé
Cancer is nowadays one of the main causes of death worldwide. The numbers have shown that one in three people will develop cancer at some point in their lives. Cancer is a major issue for the whole humanity, and therefore a lot of research has been running for the past years in order to understand the mechanisms that underlie tumorigenesis and eventually cancer formation, with the perspective to discover new approaches for effective treatment. Gene therapy strategies that intended to tackle cancer systemically are often impaired by inefficient delivery of the vector to the tumor site. Several studies have shown the possibility of using mesenchymal stem cells (MSCs) as a future therapeutic mechanism against cancer, since they possess important features such as the ability to home to and target cancer cells. The engineering of MSCs to produce and deliver an apoptotic factor, calledtumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been studied excessively. TRAIL is a transmembrane protein that causes selective apoptosis of tumor cells but does not have any harmful effects on the normal neighboring cells. Experiments have shown that this approach has significant results in mouse models and has now proceeded for clinical trials.
Résumé
@#ObjectiveTo explore the role of tumor necrosis factor related apoptosis inducing ligand (TRAIL) and it's combination with chemotherapeutic agents in treatment of cervical cancer.Methods 100μl of cervical cancer cells suspension were added to each well of 96 well plates. Cells were incubated for 24 hours with TRAIL, Adriamycin (ADM), Mitomycin C (MMC) and TRAIL combined with chemotherapeutic agents at different concentration. Rates of apoptosis and death of cells were detected by flow cytometry.ResultsRates of apoptosis of cells were 20.1% by treated with 100 μg/L TRAIL singly, which was significantly different compared with groups without agents (P<0.01). Inhibitory rates were 36.0% by treated with 10.0mg/L MMC, 44.1% by ADM. However inhibitory rates reached 58.4% or 73.7% by 100.0 μg/L TRAIL +10.0 mg/L MMC or ADM. Combined of TRAIL and MMC, TRAIL and ADM resulted in a synergistic cytotoxic effect (P<0.05).ConclusionIn vitro, TRAIL is an agent for anti cervical cancer by inducing the apoptosis of tumor cell; TRAIL can enhance the effect of ADM and MMC.