TY - JOUR T1 - Apoptosis Induced by (+)-Betulin Through NF-κB Inhibition in MDA-MB-231 Breast Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 6637 LP - 6647 DO - 10.21873/anticanres.14688 VL - 40 IS - 12 AU - GERARDO D. ANAYA-EUGENIO AU - NICOLE A. EGGERS AU - YULIN REN AU - JOSÉ RIVERA-CHÁVEZ AU - A. DOUGLAS KINGHORN AU - ESPERANZA J. CARCACHE DE BLANCO Y1 - 2020/12/01 UR - http://ar.iiarjournals.org/content/40/12/6637.abstract N2 - 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. ER -