Cytotoxic and apoptosis-inducing activity of C21 steroids from the roots of Cynanchum atratum

Jian Zhang; Lin Ma; Zheng-Feng Wu; Shu-Le Yu; Lei Wang; Wen-Cai Ye; Qing-Wen Zhang; Zhi-Qi Yin

doi:10.1016/j.steroids.2017.03.004

Cytotoxic and apoptosis-inducing activity of C₂₁ steroids from the roots of Cynanchum atratum

Steroids. 2017 Jun:122:1-8. doi: 10.1016/j.steroids.2017.03.004. Epub 2017 Mar 19.

Authors

Jian Zhang¹, Lin Ma², Zheng-Feng Wu², Shu-Le Yu², Lei Wang³, Wen-Cai Ye³, Qing-Wen Zhang⁴, Zhi-Qi Yin⁵

Affiliations

¹ Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China; Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China.
² Laboratory of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China; Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR China.
³ Institute of Traditional Chinese Medicine and Natural Products & Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou, PR China.
⁴ Institute of Chinese Medical Sciences (ICMS), University of Macau, PR China.
⁵ Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR China. Electronic address: cpu-yzq@cpu.edu.cn.

PMID: 28327355
DOI: 10.1016/j.steroids.2017.03.004

Abstract

Two new (1-2) and two known C₂₁ steroids (3-4) were isolated from the roots of Cynanchum atratum. Their structures were elucidated by detailed 1D and 2D spectroscopic. The MTT assay showed that compounds 1-4 displayed obvious cytotoxic activities against HepG2 cells with IC₅₀ values ranging from 10.19μM to 76.12μM. Compounds 1-3 also exhibited cytotoxic effects in A549 cells with IC₅₀ values of 30.87-95.39μM. Compound 3 showed the antiproliferative activity via G0/G1 cell cycle arrest and proapoptosis in HepG2 cells by Flowcytometry analysis. Western blotting analysis revealed that compound 3 could induce HepG2 cell apoptosis via the mitochondrial pathway by downregulating Bcl-2 expression, upregulating Bax protein expression, and activating caspase-9 and caspase-3.

Keywords: Apoptosis; C(21) steroids; Cynanchum atratum; Cytotoxic activity; Mitochondrial pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemistry
Antineoplastic Agents / isolation & purification
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects*
G1 Phase Cell Cycle Checkpoints / drug effects
Hep G2 Cells
Humans
Plant Roots / chemistry*
Resting Phase, Cell Cycle / drug effects
Steroids / chemistry
Steroids / isolation & purification
Steroids / pharmacology*
Vincetoxicum / chemistry*

Substances

Antineoplastic Agents
Steroids