Effect and mechanism of gerbeloid J from Gerbera piloselloides (L.) Cass. on cycle and apoptosis of breast cancer cells
10.16438/j.0513-4870.2022-1167
- VernacularTitle:毛大丁草内酯J对乳腺癌细胞周期和凋亡的影响及机制研究
- Author:
Jing-rong LI
1
;
Ling-yu LI
2
;
Chen-xu ZHAO
2
;
Hai SHANG
2
;
Tao ZHANG
2
;
Zhong-mei ZOU
2
;
Lei WAN
1
Author Information
1. School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, China
2. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union College, Beijing 100193, China
- Publication Type:Research Article
- Keywords:
breast cancer;
italic>Gerbera piloselloides (L.) Cass.;
gerbeloid J;
proliferation;
apoptosis
- From:
Acta Pharmaceutica Sinica
2023;58(4):938-945
- CountryChina
- Language:Chinese
-
Abstract:
Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.