Mitochondrial dysfunction and apoptosis-related gene activation induced by combined ethyl acetate fractions of Uncaria sp. and Selaginella doederleinii in Saccharomyces cerevisiae.

BACKGROUND: The combination of ethyl acetate fractions from Uncaria sp. and Selaginella doederleinii (EAF-BC) holds potential as an anticancer agent; however, its underlying molecular mechanism remains unclear. This study aimed to determine the anticancer potential of these combinations by evaluating the hallmarks of apoptosis using a Saccharomyces cerevisiae model. METHODS AND RESULTS: Yeast cells were incubated with EAF-BC at concentrations of 5, 10, and 100 ppm for 24 h. The analyzed parameters included petite colony frequency, mitochondrial activity, cell surface morphology, phosphatidylserine externalization, DNA fragmentation, and apoptosis-related gene regulation (FSH3, AIF1, and YCA1). The results showed that EAF-BC induced mitochondria-driven apoptosis in a dose-dependent manner. The 100-ppm concentration caused severe mitochondrial damage, yielding 85% petite colony formation, reduced mitochondrial fluorescence, surface wrinkling, phosphatidylserine externalization, and DNA fragmentation. This concentration significantly upregulated FSH3 (6-fold), YCA1 (3-fold), and AIF1 (2-fold) expression. Lower concentrations (5 and 10 ppm) also induced apoptosis, although the activity was lower. CONCLUSION: EAF-BC induced apoptosis-associated cellular changes accompanied by mitochondrial dysfunction in Saccharomyces cerevisiae, as evidenced by increased petite colony formation and multiple apoptotic hallmarks.