Chlorahololide D, a Lindenane-Type Sesquiterpenoid Dimer from Chloranthus holostegius Suppressing Breast Cancer Progression

Author:

Li Ying1,Liu Wenhui1ORCID,Xu Jing12,Guo Yuanqiang1

Affiliation:

1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300350, China

2. State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China

Abstract

Aimed at discovering small molecules as anticancer drugs or lead compounds from plants, a lindenane-type sesquiterpene dimer, chlorahololide D, was isolated from Chloranthus holostegius. The literature review showed that there were few reports on the antitumor effects and mechanisms of chlorahololide D. Our biological assay suggested that chlorahololide D blocked the growth and triggered apoptosis of MCF-7 cells by stimulating the reactive oxygen species (ROS) levels and arresting the cell cycle at the G2 stage. Further mechanism exploration suggested that chlorahololide D regulated apoptosis-related proteins Bcl-2 and Bax. Moreover, chlorahololide D inhibited cell migration by regulating the FAK signaling pathway. In the zebrafish xenograft model, chlorahololide D was observed to suppress tumor proliferation and migration significantly. Considering the crucial function of angiogenesis in tumor development, the anti-angiogenesis of chlorahololide D was also investigated. All of the research preliminarily revealed that chlorahololide D could become an anti-breast cancer drug.

Funder

National Natural Science Foundation of China

State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University

The 111 Project

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

Reference38 articles.

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4. Ciuba, A., Wnuk, K., Nitsch-Osuch, A., and Kulpa, M. (2022). Health care accessibility and breast cancer mortality in Europe. Int. J. Environ. Res. Public Health, 19.

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