Abstract
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 anticancer 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.
概要
肿瘤坏死因子相关凋亡诱导配体(TRAIL)的死亡受体可以避开P53依赖的途径来诱导肿瘤细胞凋亡而不会损害大多数正常细胞。但是,各种癌细胞可以通过不同途径对TRAIL诱导的细胞凋亡产生抗性。因此找到一种有效的TRAIL敏化剂,以逆转肿瘤细胞对TRAIL的抵抗力至关重要。同时,中药及其有效成分对治疗肿瘤方面显示出巨大的潜力。这篇综述归纳了可有效逆转肿瘤细胞对TRAIL的耐药性并增强TRAIL诱导凋亡能力的中药及其有效成分的信息,为TRAIL治疗的发展和用于人类癌症治疗的新型抗癌药物的产生提供新思路。
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Acknowledgments
This study was supported by the Guangdong Basic and Applied Basic Research Foundation (No. 2019A1515110167), China.
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Ming HONG, Wulin WEN, and Jiawei WANG conducted this review. Bingyu SUN, Yongqiang LIU, Danhua HE, and Jinke LI contributed in the writing and editing of the manuscript. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Bingyu SUN, Yongqiang LIU, Danhua HE, Jinke LI, Jiawei WANG, Wulin WEN, and Ming HONG declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Sun, B., Liu, Y., He, D. et al. Traditional Chinese medicines and their active ingredients sensitize cancer cells to TRAIL-induced apoptosis. J. Zhejiang Univ. Sci. B 22, 190–203 (2021). https://doi.org/10.1631/jzus.B2000497
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DOI: https://doi.org/10.1631/jzus.B2000497
Key words
- Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
- Cancer therapy
- Chinese medicine
- Apoptosis