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

Janviere Kabagwira,1,2 Ryan N Fuller,1,2 Paul A Vallejos,1,2 Chase S Sugiono,1 Vola-Masoandro Andrianarijaona,1 Jazmine Brianna Chism,2 Michael P O’Leary,3 David Caba Molina,3 William Langridge,1,2 Maheswari Senthil,4 Nathan R Wall1,2 1Department of Basic Science, Division of Biochemistry, Loma Linda University, Loma Linda, CA, USA; 2Center for Health Disparities and Molecular Medicine, Loma Linda University, Loma Linda, CA, USA; 3Division of Surgical Oncology, Department of Surgery, Loma Linda University Health, Loma Linda, CA, USA; 4Division of Surgical Oncology, Department of Surgery, Irvine Medical Center, University of California, Orange, CA, USACorrespondence: Nathan R Wall, Department of Basic Science, Division of Biochemistry, Loma Linda University, 11085 Campus Street, Mortensen Hall, Room 162, Loma Linda, CA, 92350, USA, Tel +1-909-558-4000 x81397, Fax +1-909-558-0177, Email nwall@llu.eduIntroduction: 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 micros