Cytotoxic and apoptosis-inducing activity of C21steroids from the roots of Cynanchum atratum.
Two new (1-2) and two known C21steroids (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 IC50values ranging from 10.19μM to 76.12μM. Compounds 1-3 also exhibited cytotoxic effects in A549 cells with IC50values 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.
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.
Jian
J
Zhang
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.
Lin
L
Ma
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.
Zheng-Feng
ZF
Wu
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.
Shu-Le
SL
Yu
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.
Lei
L
Wang
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.
Wen-Cai
WC
Ye
Institute of Chinese Medical Sciences (ICMS), University of Macau, PR China.
Qing-Wen
QW
Zhang
Department of Natural Medicinal Chemistry & State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, PR China. Electronic address: cpu-yzq@cpu.edu.cn.
Zhi-Qi
ZQ
Yin
D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D018517:Plant Roots / Q000737:chemistry*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D066047:Vincetoxicum / Q000737:chemistry*
D000970:Antineoplastic Agents; D013256:Steroids
Apoptosis; C(21) steroids; Cynanchum atratum; Cytotoxic activity; Mitochondrial pathway