Feng Ke, Li Xiaojiang, Bai Yuzhuo, Zhang Dawei, Tian Lin
Department of General Surgery, Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130000, China.
Department of Breast and Thyroid Surgery Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, 130000, China.
Heliyon. 2024 Jan 10;10(2):e24335. doi: 10.1016/j.heliyon.2024.e24335. eCollection 2024 Jan 30.
The need for naturally occurring constituents is driven by the rise in the cancer prevalence and the unpleasant side effects associated with chemotherapeutics. Triptolide, the primary active component of "Tripterygium Wilfordii", has exploited for biological mechanisms and therapeutic potential against various tumors. Based on the recent pre-clinical investigations, triptolide is linked to the induction of death of cancerous cells by triggering cellular apoptosis via inhibiting heat shock protein expression (HSP70), and cyclin dependent kinase (CDKs) by up regulating expression of P21. MKP1, histone methyl transferases and RNA polymerases have all recently identified as potential targets of triptolide in cells. Autophagy, AKT signaling pathway and various pathways involving targeted proteins such as A-disintegrin & metalloprotease-10 (ADAM10), Polycystin-2 (PC-2), dCTP pyro-phosphatase 1 (DCTP1), peroxiredoxin-I (Prx-I), TAK1 binding protein (TAB1), kinase subunit (DNA-PKcs) and the xeroderma-pigmentosum B (XPB or ERCC3) have been exploited. Besides that, triptolide is responsible for enhancing the effectiveness of various chemotherapeutics. In addition, several triptolide moieties, including minnelide and LLDT8, have progressed in investigations on humans for the treatment of cancer. Targeted strategies, such as triptolide conjugation with ligands or triptolide loaded nano-carriers, are efficient techniques to confront toxicities associated with triptolide. We expect and anticipate that advances in near future, regarding combination therapies of triptolide, might be beneficial against cancerous cells.
癌症患病率的上升以及化疗药物令人不适的副作用，推动了对天然成分的需求。雷公藤甲素是“雷公藤”的主要活性成分，已被用于研究其针对各种肿瘤的生物学机制和治疗潜力。基于最近的临床前研究，雷公藤甲素通过抑制热休克蛋白表达（HSP70）触发细胞凋亡，并上调P21的表达来抑制细胞周期蛋白依赖性激酶（CDK），从而与癌细胞死亡的诱导有关。MKP1、组蛋白甲基转移酶和RNA聚合酶最近都被确定为雷公藤甲素在细胞中的潜在靶点。自噬、AKT信号通路以及涉及靶向蛋白如A-整合素和金属蛋白酶-10（ADAM10）、多囊蛋白-2（PC-2）、dCTP焦磷酸酶1（DCTP1）、过氧化物酶-1（Prx-I）、TAK1结合蛋白（TAB1）、激酶亚基（DNA-PKcs）和着色性干皮病B（XPB或ERCC3）的各种通路已被研究。除此之外，雷公藤甲素还能增强各种化疗药物的疗效。此外，包括米内立德和LLDT8在内的几种雷公藤甲素衍生物在癌症治疗的人体研究中取得了进展。靶向策略，如将雷公藤甲素与配体结合或负载雷公藤甲素的纳米载体，是应对雷公藤甲素相关毒性的有效技术。我们期望并预计，在不久的将来，雷公藤甲素联合疗法的进展可能对癌细胞有益。
