| Yanping Gao,Zhiyong Dong,Jun Bai. A novel derivative of Genistein inhibits proliferation of ovarian cancer HO-8910 cells by regulating reactive oxygen species. Oncol Transl Med, 2022, 8: 285-292. |
| A novel derivative of Genistein inhibits proliferation of ovarian cancer HO-8910 cells by regulating reactive oxygen species |
| Received:September 10, 2022 Revised:December 29, 2022 |
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| KeyWord:ovarian cancer; 5-hydroxy-4’-nitro-7-propionyloxy-genistein; reactive oxygen species; proliferation; apoptosis |
| Author Name | Affiliation | E-mail | | Yanping Gao | The First People''s Hospital of Datong | gaoyanpingdtu@163.com | | Zhiyong Dong | The First Affiliated Hospital of Jinan University | | | Jun Bai | The First People''s Hospital of Datong | baijunjinanu@163.com |
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| Abstract: |
| Objective To investigate the anticancer effect of a novel derivative of genistein (5-hydroxy-4’-nitro-7-
propionyloxy-genistein, HNPG) on human ovarian cancer HO-8910 cells and its possible molecular
mechanism.
Methods HO-8910 cells were cultured in vitro, and the inhibitory effect of HNPG on proliferation was
determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The effect of
HNPG on inducing apoptosis was examined using FCM with Annexin V-FITC and propidium iodide staining.
The effect of HNPG on regulating reactive oxygen species (ROS) was measured using FCM with 2’,7’?di
chlorodihydro?fluorescein diacetate staining. The effect of HNPG on modulating mitochondrial membrane
potential (MMP) was determined using FCM with lipophilic cationic dye 2 (6 Amino 3 imino 3H xanthen 9
yl) benzoic acid methyl ester (Rh123) staining. The bioactivity of superoxide dismutase (SOD) and catalase
(CAT) and the content of glutathione (GSH) and malondialdehyde (MDA) were detected using enzymelinked
immunosorbent assay. The related apoptotic proteins, including bcl-2, bax, cyt-c, and cleavedcaspase-
3, were assessed using western blotting.
Results HNPG exhibited dramatic antitumor activity against HO-8910 cells in vitro, inhibited proliferation,
and induced apoptosis in a time- and dose-dependent manner. These effects were accompanied by reduced
bioactivity of SOD and CAT, reduced GSH content, and enhanced MDA content. Simultaneously, the
amount of ROS was increased and the level of MMP was reduced, along with upregulation of mitochondrial
apoptosis pathway-related proteins, bax, cyt-c, and cleaved-caspase-3; bcl-2 protein was downregulated.
Conclusion HNPG inhibited proliferation of human ovarian cancer HO-8910 cells in vitro, which might
be related to decreased bioactivity of SOD and CAT. HNPG also reduced GSH content, which resulted in
ROS accumulation in cells, damaged the integrity of mitochondrial membrane, and induced cell apoptosis |
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