Hederagenin suppresses ovarian cancer via targeting mitochondrial fission through dynamin-related protein 1

Su, Fang1; Sui, Xin1; Xu, Jiabao1; Liu, Qingling1; Li, Junfeng1; Liu, Wenhong1; Xu, Ye1; Zhang, Zhiqian2,4; Tao, Fangfang1,3

2024-01-15

10.1016/j.ejphar.2023.176188

EUROPEAN JOURNAL OF PHARMACOLOGY   影响因子和分区

0014-2999

1879-0712

A triterpenoid isolated from the plant Hedera helix, hederagenin was discovered to have anti-cancer, anti-inflammatory, anti-depressant and anti-fibrosis properties both in vivo and in vitro. In this study, the relationship between mitochondrial fission and hederagenin-induced apoptosis in ovarian cancer (OC) was investigated and the underlying mechanisms were deciphered. Hederagenin's cytotoxicity on OC cells was analyzed using colony formation and CCK-8 assays. The effect of hederagenin on OC cells was also verified by a mouse xenograft tumor model. Flow cytometric analysis was conducted to examine hederagenin's effects on mitochondrial membrane potential, apoptosis, and cell cycle OC cells. MitoTracker Red (CMXRos) staining was performed to observe the mitochondrial morphology. The protein levels of Bak, Bcl-2, Caspase 3, Caspase 9, Cyclin D1 and Bax were measured by Western blot. This study found that hederagenin could suppress the in vivo and in vitro SKOV3 and A2780 cell proliferation in an effective manner. Besides, hederagenin altered the mitochondrial membrane potential, induced S-phase and G0/G1-phase arrest, mitochondrial morphology changes, and apoptosis in OC cells. Additionally, our findings further demonstrated that hederagenin changed the mitochondrial morphology by suppressing dynamin-related protein 1 (Drp1), a crucial mitochondrial division factor. Moreover, Drp1 overexpression could reverse hederagenin-induced apoptosis, whereas the Drp1 knockdown had the opposite effect. Furthermore, hederagenin may trigger BAX mitochondrial translocation and apoptosis in OC cells. These results provided a novel perspective on the relationship between the modulation of mitochondrial morphology and the suppression of ovarian cancer by hederagenin.

Hederagenin Drp1 Mitochondria morphology Apoptosis Ovarian cancer

SCI

英语

通讯

National Natural Science Foundation of China["82074391","32170568","82002997"] ; Zhejiang Provincial Natural Science Foundation of China[LY21H270004] ; Youth Project of Zhejiang Administration of Traditional Chinese Medicine[2019ZQ013] ; General Project of Basic Research in Shenzhen[JCYJ20190809161215057] ; Medical Scientific Research Foundation of Guangdong Province of China[A2022131]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:001147347100001

ELSEVIER

PHARMACOLOGY & TOXICOLOGY

Web of Science

1.Zhejiang Chinese Med Univ, Sch Basic Med Sci, Dept Immunol & Microbiol, 548 Binwen Rd, Hangzhou 310053, Zhejiang, Peoples R China
2.Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China
3.Key Lab Blood Stasis Toxin Syndrome Zhejiang Prov, Hangzhou 310053, Zhejiang, Peoples R China
4.Southern Univ Sci & Technol, Sch Med, Shenzhen, Peoples R China

Su, Fang,Sui, Xin,Xu, Jiabao,et al. Hederagenin suppresses ovarian cancer via targeting mitochondrial fission through dynamin-related protein 1[J]. EUROPEAN JOURNAL OF PHARMACOLOGY,2024,963.

Su, Fang.,Sui, Xin.,Xu, Jiabao.,Liu, Qingling.,Li, Junfeng.,...&Tao, Fangfang.(2024).Hederagenin suppresses ovarian cancer via targeting mitochondrial fission through dynamin-related protein 1.EUROPEAN JOURNAL OF PHARMACOLOGY,963.

Su, Fang,et al."Hederagenin suppresses ovarian cancer via targeting mitochondrial fission through dynamin-related protein 1".EUROPEAN JOURNAL OF PHARMACOLOGY 963(2024).