RT Journal Article
SR Electronic
T1 Apoptosis Induced by (+)-Betulin Through NF-κB Inhibition in MDA-MB-231 Breast Cancer Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 6637
OP 6647
DO 10.21873/anticanres.14688
VO 40
IS 12
A1 GERARDO D. ANAYA-EUGENIO
A1 NICOLE A. EGGERS
A1 YULIN REN
A1 JOSÉ RIVERA-CHÁVEZ
A1 A. DOUGLAS KINGHORN
A1 ESPERANZA J. CARCACHE DE BLANCO
YR 2020
UL http://ar.iiarjournals.org/content/40/12/6637.abstract
AB 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.