EXPLORING THE ROLE OF BIOACTIVE PHYTOCHEMICALS IN CANCER CELL APOPTOSIS AND CELL CYCLE ARREST MECHANISMS

Abstract

This study investigates the mechanistic role of selected bioactive phytochemicals—curcumin, quercetin, and resveratrol—in inducing apoptosis and cell cycle arrest in human cancer cell lines, with the objective of identifying effective, low-toxicity alternatives to conventional chemotherapeutics. Using MCF-7 (breast), HCT-116 (colon), and PC-3 (prostate) cancer cells, we conducted a series of in vitro assays to assess cytotoxicity, apoptotic activity, cell cycle distribution, reactive oxygen species (ROS) generation, mitochondrial membrane potential disruption, and changes in regulatory protein expression. IC₅₀ determination revealed that curcumin exhibited the highest cytotoxic potency across all tested cell lines. Flow cytometry confirmed significant induction of early and late apoptosis, particularly in curcumin-treated groups, with HCT-116 cells showing the greatest apoptotic shift. Cell cycle analysis indicated a pronounced arrest at the G0/G1 phase, especially in MCF-7 and HCT-116 cells. Western blotting demonstrated upregulation of caspase-3 and Bax, along with downregulation of Bcl-2 and Cyclin D1, accompanied by increased p21 expression, indicating dual pro-apoptotic and anti-proliferative actions. Quantitative PCR validated these protein expression trends at the transcript level. Furthermore, DCFH-DA and JC-1 assays revealed significant ROS accumulation and mitochondrial membrane depolarization, confirming mitochondrial pathway involvement in apoptosis. Notably, curcumin led to the highest ROS generation (185%) and Δψm loss (71%) among the compounds. These findings substantiate the potential of plant-derived phytochemicals as multi-targeted agents capable of selectively inducing cancer cell death while halting proliferation. This research not only enhances mechanistic understanding of phytochemical action but also provides foundational data for advancing these compounds toward clinical translation as complementary cancer therapies.