Evaluation of the Combinatory Anticancer Effect of Chemotherapeutic Compounds and Prodigiosin against HCT-116, LoVo, and A549 Cell lines

Despite their wide usage in reducing tumors and improving patients' survival, chemotherapeutic drugs or natural compounds are facing the development of cancer resistance. Many experimental data and clinical trials have shown that combinatorial treatment could be an efficient solution for some resistance problems. In this study, we aimed to evaluate the synergistic effects of combining prodigiosin (PG), a natural compound with known anticancer properties, with the commonly used chemotherapy drugs 5-fluorouracil (5-FU), oxaliplatin, and paclitaxel. The primary objective was to identify the most potent combination that could enhance tumor cytotoxicity while minimizing drug resistance. <i>In vitro</i> experiments using three cancer cell lines (LoVo, HCT-116, and A549) were conducted to assess the impact of these combinations on the cell viability and proliferation. Recorded data demonstrated that the combination of 20 μM PG with 1/2 IC50 of 5-FU showed the most significant decrease in cell viability, with remaining viabilities of 28, 32, and 43% for LoVo, HCT-116, and A549 cells, respectively. This combination resulted in a notable increase in the proportion of cells in the G0/G1 phase and a decrease in the S phase of the cell cycle. These findings indicated that this combination effectively induced cell-cycle arrest. In contrast, other combinations such as PG with paclitaxel or oxaliplatin were less effective. Furthermore, molecular docking studies revealed that PG targets Akt1, a key protein in the PI3K/Akt survival pathway, providing a possible explanation for its proapoptotic effects. These findings suggested that the combination of PG with 5-FU enhanced tumor cell sensitivity to chemotherapy, potentially offering a more effective treatment strategy for overcoming drug resistance. In conclusion, the current study highlighted the promising potential of PG in combination with 5-FU as a therapeutic approach for colorectal and lung cancers, warranting further investigations in preclinical and clinical settings.