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.