Abstract
BACKGROUND: Cervical cancer remains the fourth most common malignancy among women worldwide, with limited therapeutic success in advanced and recurrent stages. Conventional treatments, including radiotherapy and chemotherapeutic agents are often limited by off-target toxicity and poor selectivity toward malignant cells. Considering growing interest in phytotherapeutics, the present study evaluates the cytotoxic and genotoxic effects of methanolic extract of Curcuma caesia (MECC) on cervical cancer cells. METHODS: Human cervical cancer cell lines (HeLa and SiHa) and non-cancerous HEK293T cells were treated with varying concentrations of MECC. Cell viability, proliferation, and oxidative stress were assessed via MTT, cell cycle analysis, and ROS quantification, respectively. DNA damage and repair responses were evaluated using COMET, TUNEL, and γH2A.X foci assays. Senescence was detected by β-galactosidase staining, while apoptotic and DNA damage response proteins were examined through Western blotting. RESULTS: MECC exhibited dose-dependent cytotoxicity in HeLa and SiHa cells while sparing HEK293T cells, indicating selectivity toward malignant cells. Treatment induced cell cycle arrest and significantly reduced intracellular ROS levels. DNA damage was evident from increased comet tail moments, TUNEL positivity, and nuclear accumulation of γH2A.X. MECC further promoted apoptosis, as demonstrated by elevated levels of cleaved caspase-3, Bax, cleaved PARP1, and reduced Bcl-2 expression. Concurrent induction of cellular senescence was also observed. CONCLUSION: MECC induces apoptosis and senescence, through modulation of oxidative stress and induction of DNA damage in cervical cancer cells. This highlights its potential as a plant-based therapeutic candidate with reduced cytotoxicity toward non-cancerous cells. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-026-05351-0.