Apoptosis Induced by (+)-Betulin Through NF-κB Inhibition in MDA-MB-231 Breast Cancer Cells
Gerardo D Anaya-Eugenio1, Nicole A Eggers1, Yulin Ren1
1Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH, U.S.A.
Background/Aim:
This study aimed to uncover the effects of (+)-betulin on the NF-κB-apoptotic pathway in MDA-MB-231 cells, and determine its toxicity and protein expression in vivo.
Materials And Methods:
Cell cytotoxicity and toxicity were determined using the SRB assay and a zebrafish model, respectively. Western blot, mitochondrial transmembrane potential (MTP), and computational modeling analysis were performed.
Results:
(+)-betulin inhibited the growth of MDA-MB-231 cells, but did not induce toxicity in zebrafish. (+)-Betulin inhibited the activity of NF-κB p65 in silico and in vitro. In cells, (+)-betulin down-regulated NF-κB p50 and 65, IKKα and β, ICAM-1 and bcl-2 expressions. Cell co-treatment with (+)-betulin and TNFα increased the (+)-betulin cytotoxic potential. Moreover, (+)-betulin induced the loss of MTP. Furthermore, (+)-betulin, in zebrafish, down-regulated the expression of NF-κB p65, IKKα, ΙΚΚβ and procaspase-3.
Conclusion:
The results contribute to the understanding of the mode of action on apoptosis induction by inhibiting NF-κB pathway in MDA-MB-231 cells.
Insights
(+)-Betulin effectively inhibits MDA-MB-231 cancer cell growth by targeting the NF-κB pathway. This natural compound shows promise as it does not induce toxicity in zebrafish models, offering a potential therapeutic avenue.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- The NF-κB pathway plays a crucial role in cell survival and inflammation.
- MDA-MB-231 cells are a triple-negative breast cancer cell line.
- (+)-Betulin is a natural compound with potential anti-cancer properties.
Purpose of the Study:
- To investigate the effects of (+)-betulin on the NF-κB-apoptotic pathway in MDA-MB-231 cells.
- To assess the in vivo toxicity and protein expression of (+)-betulin using a zebrafish model.
Main Methods:
- Cytotoxicity was evaluated using the SRB assay.
- In vivo toxicity was assessed in a zebrafish model.
- Western blot, mitochondrial transmembrane potential (MTP) analysis, and computational modeling were employed.
Main Results:
- (+)-Betulin inhibited MDA-MB-231 cell growth without causing zebrafish toxicity.
- (+)-Betulin suppressed NF-κB p65 activity in silico and in vitro.
- Down-regulation of NF-κB p50/p65, IKKα/β, ICAM-1, and bcl-2 was observed in cells; MTP loss was induced.
Conclusions:
- (+)-Betulin induces apoptosis in MDA-MB-231 cells by inhibiting the NF-κB pathway.
- The findings contribute to understanding the anti-cancer mechanism of (+)-betulin.
- The study supports the potential of (+)-betulin as a therapeutic agent.
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