The Synergistic Antitumor Effects of Curcuma longa and Phyllanthus niruri Extracts on Promoting Apoptotic Pathways in Breast Cancer Stem Cells

Munir D., Putra A., Amalina N.D., Alif I., Hermansyah D., Lelo A.

Abstract

Breast cancer stem cells (BCSCs) develop apoptosis resistance by expressing pro-and anti-apoptotic protein including caspase-3, p53, and survivin. However, the induction of apoptosis is an important mechanism of action for many anticancer agents. Therefore, treatment using combination therapy was supposed to inhibit apoptosis resistance and increase the possibility of cancer apoptosis. This study aimed to investigate the effects of the combination Curcuma longa (CL) and Phyllanthus niruri (PN) extract on apoptosis induction. The single and combination cytotoxicity was analyzed using MTT assay. Apoptosis was measured by Annexin V-Propidium Iodide under flow cytometry. Caspase 3 expression was assessed by flow cytometry. p53 protein synthesis analyzed under qRT-PCR and survivin expression level was determined by immunocytochemistry. CL and PN inhibited BCSCs cell growth with IC50 value of 113 and 500 µg/mL, respectively. The combination of CL 30 and 60 µg/mL with PN 31.25 µg/mL has a synergistic effect by apoptosis induction up to 99.90% and 100%, respectively. The combination also significantly increased the expression of caspase-3 and p53. Interestingly, the combination significantly decreased the survivin levels in a dose-dependent manner. In conclusion, the combination of CL and PN can induce apoptosis by increasing the caspase-3 and p53 protein level and decreasing surviving expression in BCSCs.

Journal
Thai Journal of Pharmaceutical Sciences
Page Range
541-550
Publication date
2022
Total citations
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