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13-Ethylberberine Induces Apoptosis through the Mitochondria-Related Apoptotic Pathway in Radiotherapy-Resistant Breast Cancer Cells.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2019 Jul 04; Vol. 24 (13). Date of Electronic Publication: 2019 Jul 04. - Publication Year :
- 2019
-
Abstract
- Berberine is reported to have multiple biological effects, including antimicrobial, anti-inflammatory, and antitumor activities, and 13-alkyl-substituted berberines show higher activity than berberine against certain bacterial species and human cancer cell lines. In particular, 13-ethylberberine (13-EBR) was reported to have anti-inflammatory effects in endotoxin-activated macrophage and septic mouse models. Thus, in this study, we aimed to examine the anticancer effects of 13-EBR and its mechanisms in radiotherapy-resistant (RT-R) MDA-MB-231 cells derived from the highly metastatic MDA-MB-231 cells. When we compared the gene expression between MDA-MB-231 and RT-R MDA-MB-231 cells with an RNA microarray, RT-R MDA-MB-231 showed higher levels of anti-apoptotic genes and lower levels of pro-apoptotic genes compared to MDA-MB-231 cells. Accordingly, we examined the effect of 13-EBR on the induction of apoptosis in RT-R MDA-MB-231 and MDA-MB-231 cells. The results showed that 13-EBR reduced the proliferation and colony-forming ability of both MDA-MB-231 and RT-R MDA-MB-231 cells. Moreover, 13-EBR induced apoptosis by promoting both intracellular and mitochondrial reactive oxygen species (ROS) and by regulating the apoptosis-related proteins involved in the intrinsic pathway, not in the extrinsic pathway. These results suggest that 13-EBR has pro-apoptotic effects in RT-R MDA-MB-231 and MDA-MB-231 cells by inducing mitochondrial ROS production and activating the mitochondrial apoptotic pathway, providing useful insights into new potential therapeutic strategies for RT-R breast cancer treatment.
- Subjects :
- Berberine chemistry
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Mitochondria drug effects
Models, Biological
Reactive Oxygen Species metabolism
Up-Regulation drug effects
Apoptosis drug effects
Berberine pharmacology
Breast Neoplasms pathology
Breast Neoplasms radiotherapy
Mitochondria metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 24
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 31277363
- Full Text :
- https://doi.org/10.3390/molecules24132448