Combined Lactobacillus Postbiotics with Carrageenan and Soy Protein Induce Sustained Apoptosis Through Multi-Pathway Survival Disruption in Colon Cancer Cells

Background: Colorectal cancer remains a major cause of cancer-related mortality, highlighting the need for effective and low-toxicity therapeutic approaches. This study examined the time-dependent anticancer effects of Lactobacillus postbiotics alone and in combination with a carrageenan/soy protein blend in HCT-116 colorectal cancer cells. Methods: Cells were divided into three groups: untreated control (NH), postbiotics alone (LPH), and the combined formulation (LPCS). Cell viability, morphological alterations, apoptotic stages, gene expression, and temporal gene–gene correlations were analyzed at 24, 48, and 72 h. Results: The combined formulation induced the strongest and most sustained cytotoxic effects, with maximal late apoptosis and necrosis observed at 72 h. Postbiotics alone mainly triggered early apoptosis at 24 h, which diminished over time. Dynamic, time-dependent modulation of apoptotic regulators (BAX and BCL2), inflammatory signaling (NF- κB), and survival-related pathways (Notch-1, Notch-2, JAG-1, HES-1, and CXCR4) were observed. Combination treatment led to early stress responses followed by suppression of survival signaling and terminal disruption of apoptotic balance. Conclusion: These findings demonstrate that combining Lactobacillus postbiotics with carrageenan and soy protein enhances both the potency and durability of anticancer effects, supporting the development of multi-component postbiotic strategies for colorectal cancer.