Caffeine Modulates Cell Death and Telomerase Activity in Triple-negative Breast Cancer Cells

Triple-negative breast cancer (TNBC) is an aggressive subtype defined by the lack of estrogen receptors (ER), progesterone receptors (PR), and HER2 expression, resulting in limited therapeutic options. Given this challenge, this study explores caffeine, a widely consumed stimulant, as a potential anticancer agent, particularly for TNBC. Although caffeine has demonstrated stimulatory and inhibitory effects on telomerase in other cancer types, its influence on telomerase activity in TNBC remains uncharacterized. This study investigates the impact of caffeine concentrations (10, 15, and 20 mM) on cell viability, proliferation, apoptosis, ultrastructure, and the expression of apoptosis-related genes (BAX, BCL2, CASP8) and telomerase activity (hTERT) in MDA-MB-231 cells. Our findings showed that caffeine significantly reduces cell viability and induces early apoptosis with a dose-dependent effect. Morphological changes consistent with early apoptosis were observed, and an increased BAX/BCL2 ratio indicated the activation of the intrinsic apoptosis pathway. Additionally, caffeine exhibited upregulation of hTERT mRNA expression, which may reflect a compensatory response to cellular stress induced by caffeine. These results underscore the multifaceted effects of caffeine on TNBC cells, highlighting its potential not only as an apoptosis inducer but also as a modulator of telomerase activity. Given its accessibility, low toxicity, and established safety profile, caffeine presents an exciting avenue for further research as a complementary or standalone therapeutic strategy for TNBC.