Apoptosis-mediated antiproliferative activity of friedolanostane triterpenoid isolated from the leaves of Garcinia celebica against MCF-7 human breast cancer cell lines

从藤黄叶中分离的 Friedolanostane 三萜类化合物对 MCF-7 人乳腺癌细胞系具有凋亡介导的抗增殖活性

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作者:Anas Subarnas, Ajeng Diantini, Rizky Abdulah, Ade Zuhrotun, Patria A Nugraha, Yuni E Hadisaputri, Irma M Puspitasari, Chiho Yamazaki, Hiroyuki Kuwano, Hiroshi Koyama

Abstract

The leaves of Garcinia celebica strongly inhibit the proliferation of MCF-7 human breast adenocarcinoma cell lines. The present study focused on investigating the active anticancer and antiproliferative compound from the G. celebica leaves and assessing its mechanism of action. Ethanol extracts of G. celebica were fractionated based on their polarity using n-hexane, ethyl acetate and water. The antiproliferative properties were tested in vitro against MCF-7 human breast cancer cell lines using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. The active compound was subsequently isolated using column chromatography and identified by nuclear magnetic resonance. The characterized compound was also tested for its antiproliferative properties and the mechanism by which it induces apoptosis in MCF-7 cells by western blot analysis of the activated apoptotic proteins. This resulted in the isolation of a friedolanostane triterpenoid, which was determined to be methyl-3α, 23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat. This compound inhibited MCF-7 cell proliferation in a time- and dose-dependent manner with IC50 values of 82 and 70 µM for the 24 and 48 h treatments, respectively. Furthermore, the western blot analysis suggested that the compound exerted its anticancer activities by promoting apoptosis through the inhibition of the oncogenic protein Akt, thereby increasing the expression of poly (ADP-ribose) polymerase (PARP) protein. These results suggest that methyl-3α,23-dihydroxy-17,14-friedolanstan-8,14,24-trien-26-oat is the anticancer compound found in G. celebica, providing a basis for its potential use in cancer disease management.

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