Peran Propolis Sebagai Induktor Apoptosis pada Sel Osteosarkoma (U2OS) Melalui Ekspresi BCL-2, BAX, DAN CASPASE-3 In-Vitro

Abstract

Introduction: Propolis, as a natural product with antitumor properties, is considered to have potential as an apoptotic agent against osteosarcoma cells through the regulation of Bcl-2, Bax, and caspase-3 expression, but the effectiveness of Indonesian propolis on U2OS cell lines has not been widely studied. This study aims to assess the effectiveness of Indonesian propolis as an apoptosis inducer in osteosarcoma cells (U2OS) by comparing the expression of Bax, Bcl-2, and caspase-3 when given doxorubicin (standard therapy), propolis, and a combination of propolis with doxorubicin. Methods: This study used U2OS osteosarcoma cell cultures cultured in DMEM media with the addition of FBS, L-glutamine, and antibiotics, and through the process of thawing, subculture, and planting into well plates. The combination of propolis and doxorubicin was then tested on U2OS cells to assess the synergistic effect on viability and apoptotic gene expression using the MTT assay and RT-PCR methods. Results: This study showed that 10% propolis and 5 μM doxorubicin has significant differences in optical density parameters, inhibition, and Bax and Bcl-2 gene expression (p < 0.001) between groups. The combination of both also increased Bax expression and decreased Bcl-2 expression, but did not provide a significant difference in caspase-3 expression between groups (p = 0.75). Conclusion: This study shows that propolis has significant anticancer effects against osteosarcoma cells by increasing Bax expression, decreasing Bcl-2 expression, and inhibiting cell viability, especially in the combination of 10% propolis and 5 μM doxorubicin. However, in vivo research is still needed in the form of pharmacokinetic and pharmacodynamic tests on experimental animals.