Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 347, Issue -, Pages -Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2021.109619
Keywords
Melanoma; A375SM; A375P; Nuclear factor-kappa B (NF-kappa B); Apoptosis; Anticancer effects
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [NRF 2017R1A2B4005516]
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OA treatment leads to induction of apoptosis in melanoma cells through increased apoptotic bodies and decreased expression of antiapoptotic proteins such as Bcl-2.
Owing to the ineffectiveness of the currently used therapies against melanoma, there has been a shift in focus toward alternative therapies involving the use of natural compounds. This study assessed the anticancer effects of oleanolic acid (OA) and its ability to induce apoptosis in A375SM and A375P melanoma cells in vivo. Compared to the control group, viability of A375P and A375SM cells decreased following OA treatment. In OA-treated A375SM and A375P cells, 4',6-diamidino-2-phenylindole staining showed an increase in the apoptotic body, and flow cytometry revealed increased number of apoptotic cells compared to that in the control group. OA-treated A375SM cells exhibited an increased expression of the apoptotic proteins, cleaved poly (ADP-ribose) polymerase (PARP) and B-cell lymphoma (Bcl)-2-associated X protein (Bax) as well as decreased expression of the antiapoptotic protein Bcl-2 compared to that in the control group. In OA-treated A375P cells, expression patterns of cleaved PARP and Bcl-2 were similar to those in OA-treated A375SM cells; however, no difference was reported in the expression of Bax compared to that in the control group. Additionally, OA-treated melanoma cells showed decreased expression of phospho-nuclear factor-kappa B (p-NF-kappa B), phospho-inhibitor of nuclear factorKBa (p-I kappa B alpha), and phospho-I kappa B kinase alpha beta than that in the control group. Moreover, immunohistochemistry showed a comparatively decreased level of p-NF-kappa B in the OA-treated group than that in the control group. Xenograft analysis confirmed the in vivo anticancer effects of OA against A375SM cells. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay revealed an increased number of TUNEL-positive cells in the OA-treated group compared to that in the control group. In conclusion, the study results suggest that OA induces apoptosis of A375SM and A375P cells in vitro and apoptosis of A375SM cells in vivo. Furthermore, the in vitro and in vivo anticancer effects were mediated by the NF-kappa B pathway.
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