(5R)-5-hydroxytriptolide (LLDT-8), a novel immunosuppressant in clinical trials, exhibits potent antitumor activity via transcription inhibition

Cancer Letters
Lei WangLiguang Lou

Abstract

(5R)-5-hydroxytriptolide (LLDT-8), a triptolide derivative, is a low-toxicity immunosuppressant in Phase I clinical trials. Here, we demonstrate that LLDT-8 displays broad-spectrum, potent (nanomolar level IC(50)s) antitumor activity, and induces S-phase cell-cycle arrest and apoptosis in vitro. Notably, LLDT-8 effectively overcomes multidrug resistance mediated by P-glycoprotein. In vivo, LLDT-8 demonstrates potent antitumor activity, particularly against human ovarian cancer 3AO and prostate cancer PC-3 xenografts in nude mice. The antitumor activity of LLDT-8 is achieved by virtue of its general inhibition of gene transcription. Our results indicate that LLDT-8 is a novel transcription inhibitor with potential for cancer therapy, particularly for cancers with drug resistance mediated by P-glycoprotein.

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Citations

Jul 3, 2013·Cancer Letters·Quanren WangLiguang Lou
Jun 12, 2016·Journal of Pharmacological Sciences·Yanke ChenJia Jia
Jan 27, 2018·International Journal of Molecular Sciences·Danping FanXiaojuan He
Jun 24, 2020·Chemical Biology & Drug Design·He Zhang, Gongxi Lu
Nov 5, 2020·Natural Product Reports·Lu TongJun O Liu

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