Abstract Title:

A Bioreductive Prodrug of Cucurbitacin B Significantly Inhibits Tumor Growth in the 4T1 Xenograft Mice Model.

Abstract Source:

ACS Med Chem Lett. 2019 Oct 10 ;10(10):1400-1406. Epub 2019 Sep 10. PMID: 31620225

Abstract Author(s):

Parichat Suebsakwong, Jie Wang, Phorntip Khetkam, Natthida Weerapreeyakul, Jing Wu, Yun Du, Zhu-Jun Yao, Jian-Xin Li, Apichart Suksamrarn

Article Affiliation:

Parichat Suebsakwong


Cucurbitacin B (CuB), a highly cytotoxic constituent of the Cucurbitaceae plant, was identified to exhibit potent inhibitory activity against human cancer cells as well as normal cells. This disadvantage hampers the possibility of developing this compound into an anticancer drug candidate. In this work, several bioreductive prodrugs of CuB were designed to reduce toxicity to normal cells while maintaining the cytotoxic effect to cancer cells. Embedded with a bioreductive delivery and cleavable system in cancer tissues, cucurbitacin B-based prodrugs,, andwere synthesized and evaluated byandexperiments. Compared with the parent CuB, prodrugwas found to significantly reduce the toxicity down to 310-fold lower against noncancerous cells. LC-MS analyses show that prodrugefficiently releases the parent compound in the reductase-overexpressed MCF-7 cells. In addition, prodrugshows satisfactory and comparable effectiveness in controlling tumor growth as that by tamoxifen in the 4T1 xenograft mice model.

Study Type : Animal Study, In Vitro Study

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