In Vitro and in Vivo Antitumor Effects of Plant-Derived Miliusanes and Their Induction of Cellular Senescence

Xin Ya Xu, Siu Wai Tsang, Yi Fu Guan, Kang Lun Liu, Wen Hui Pan, Chu Shing Lam, Kwan Ming Lee, Yi Xuan Xia, Wen Jian Xie, Wing Yan Wong, Magnolia Muk Lan Lee, William Chi Shing Tai, Hong Jie Zhang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

Our earliest phytochemical separation of Miliusa sinensis aided us in the isolation of a class of unique miliusanes, which were demonstrated as anticancer lead molecules. In the present study, we isolated 19 miliusanes (1-19), including 11 novel ones (5 and 10-19) from another Miliusa plant (M. balansae), and synthesized additional derivatives to elucidate the structure-activity relationship of miliusanes. When extrapolated to various carcinoma xenograft mouse models, miliusol (1) and its derivatives 20, 26, and 27 (7.5-40 mg/kg) were demonstrated with tumor inhibitory efficacy comparable or even superior to the mainstay chemotherapeutics paclitaxel or fluorouracil. To gain a molecular insight into their anticancer mechanism, 1-3 (GI 50 0.03-4.79) were administered to a wide spectrum of human cancer cell lines, including those with specific drug resistance. We further revealed that the antiproliferative properties of miliusanes in carcinoma cells were highly associated with the p21-dependent induction of cellular senescence.

Original languageEnglish
Pages (from-to)1541-1561
Number of pages21
JournalJournal of Medicinal Chemistry
Volume62
Issue number3
DOIs
Publication statusPublished - 14 Feb 2019

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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