Abstract
This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8–17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.
Highlights
The genus Cimicifuga has been widely used all over the world and since ancient times has been a traditional Chinese herbal medicine
MCF-7 breast cancer cells were exposed to epidermal growth factor (EGF) which was known as a stimulator of proliferation
The cell cycle arrest at G0/G1 phase was reversed by a pan caspase inhibitor or a caspase 3 inhibitor but not the nucleoside addition. These results demonstrated that pan caspase and caspase 3 maybe had major roles in the mechanism of cell cycle arrest effects of compound 7 on MCF-7 cells
Summary
The genus Cimicifuga ( known as Actaea) has been widely used all over the world and since ancient times has been a traditional Chinese herbal medicine. This genus consists of 28 species worldwide [1], among which nine species are indigenous to China. In traditional Chinese medicine, Shengma is widely used for treating aphtha, sore throat, toothache, and wind-heat headache. It has been used in archoptosis, non-erupting measles, spot poison, uterine prolapse, and other diseases [1,2,3,4].
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