Amplifying Curcumin’s Antitumor Potential: A Heat-Driven Approach for Colorectal Cancer Treatment

Introduction: Peritoneal metastases from colorectal cancer (CRC) present a significant clinical challenge with poor prognosis, often unresponsive to systemic chemotherapy. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment approach for select patients. The use of curcumin, a natural compound with antitumor properties, in HIPEC is of interest due to its lower side effects compared to conventional drugs and potential for increased efficacy through direct delivery to the peritoneal cavity.
Methods: An in vitro hyperthermic model was developed to simulate clinical HIPEC conditions. Three colon cancer cell lines (SK-CO-1, COLO205, SNU-C1) representing different genetic mutations (p53, KRAS, BRAF) were treated with either curcumin (25 μM) or mitomycin-C (1 μM) for 1, 2, or 3 hours. Post-treatment, cells were incubated at 37°C (normothermia) or 42°C (hyperthermia). Cell viability and proliferation were assessed at 24, 48 and 72 hours post-treatment using Annexin V/PI, MTT assay, trypan blue exclusion, and Hoffman microscopy.
Results: Hyperthermia significantly enhanced the antitumor efficacy of curcumin, evidenced by a two-fold reduction in cell viability compared to normothermia across all cell lines. In the SNU-C1 cell line, which harbors a p53 mutation, mitomycin-C failed to significantly impact cell viability, unlike curcumin, suggesting mutation-specific differences in treatment response.
Discussion: The findings indicate that hyperthermia augments the antitumor effects of curcumin in vitro, supporting the hypothesis that curcumin could be a more effective HIPEC agent than traditional drugs like mitomycin-C. Mutation-associated differences in response to treatments were observed, particularly in p53 mutant cells. While further studies are needed, these preliminary results suggest that curcumin in HIPEC could represent a novel therapeutic strategy for CRC patients with peritoneal metastases. This approach may offer improved outcomes with fewer side effects, particularly in genetically distinct CRC subtypes.

Plain Language Summary: In this study, we aimed to improve treatments for peritoneal carcinomatosis (PC), a challenging form of colorectal cancer (CRC) that does not respond well to regular chemotherapy. We explored an approach called hyperthermic intraperitoneal chemotherapy (HIPEC), which involves delivering potent chemotherapy directly to the abdominal area at an elevated temperature. Our innovative idea was to enhance HIPEC’s effectiveness by using curcumin, a natural compound with fewer side effects than conventional HIPEC drugs. To test our theory, we conducted experiments on colon cancer cells under high-temperature conditions, mimicking what occurs during HIPEC treatments. We also compared curcumin with the standard drug, mitomycin-C (MMC). We discovered that curcumin, when delivered under high temperatures, outperformed MMC in killing colorectal cancer cells. This is an exciting breakthrough because it suggests that curcumin in HIPEC could be a promising alternative for treating PC. While we are still working on more comparisons and further studies, this outcome represents a significant step towards better treatment options for patients with peritoneal carcinomatosis. In conclusion, our study was motivated by the need to find more effective ways to combat an aggressive form of colorectal cancer metastasis. By exploring the potential of curcumin in HIPEC, we hope to provide better treatment options for patients who face this challenging disease.

Keywords: peritoneal carcinomatosis, curcumin, hyperthermic, colorectal, mitomycin-C