Modulation Of Beclin-1 and Bcl-2 Expression by Intermittent Fasting In CRC: Links to Autophagy and Apoptosis (Research Article))

Author(s): K Pavan Kumar* and Amit Kumar

Abstract: Colorectal cancer (CRC) represents a leading cause of cancer-related morbidity and mortality worldwide, driven by the dysregulation of signaling pathways controlling autophagy and apoptosis. The present study investigates the mechanistic influence of intermittent fasting (IF) on the modulation of Beclin-1 and Bcl-2—key regulators linking autophagy and apoptosis—in a colorectal cancer rat model. Experimental animals were divided into seven groups, including controls, fasting durations (6, 12, 18, and 24 hours), and a standard drug treatment group. Aberrant crypt foci (ACF) quantification, histopathology, immunohistochemistry, TUNEL assay, Western blotting, ELISA, qRT-PCR, and molecular analyses were performed to evaluate the effects of IF on cellular and biochemical markers. IF induced a time-dependent modulation of Beclin-1 and Bcl-2 expression, with 24-hour fasting showing the highest expression intensity. Significant reductions in pro-inflammatory proteins (NF-κB, TNF-α, IL-6) and oxidative stress markers were observed, accompanied by restoration of antioxidant enzymes (SOD, CAT, GSH, GPx) and normalization of Caspase-3 activity. These findings demonstrate that intermittent fasting enhances autophagic clearance and sensitizes tumor cells to apoptosis by rebalancing Beclin-1/Bcl-2 signaling and reducing inflammatory stress. Thus, IF may serve as a promising metabolic intervention for colorectal cancer prevention and adjunct therapy by targeting molecular crosstalk between autophagy and apoptosis.

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