Abstract 1451: Hyperthermic conditions improve curcumin efficacy for the treatment of peritoneal carcinomatosis of colon cancer origin

Abstract

Abstract Patients with peritoneal metastases from colorectal cancer (CRC) have poor prognosis. Systemic chemotherapy by itself is often ineffective in the treatment of peritoneal carcinomatosis. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is offered to appropriately selected patients. HIPEC consists of direct application of high-dose chemotherapy to the peritoneal cavity under hyperthermic conditions for 90-120 minutes. Although there is strong evidence to demonstrate improved survival with cytoreductive surgery, the role of HIPEC needs further evaluation. Furthermore, despite optimal cytoreduction, a subset of patients will suffer early peritoneal recurrence which indicates that the intraperitoneal chemotherapy was ineffective in controlling the microscopic disease. In vitro studies focused on optimizing the drug, duration of exposure, and temperature based on the biology of the cancer are critically needed to inform the design of future clinical trials. The combination of the HIPEC treatment modality with curcumin as the therapeutic agent is attractive since the naturally occurring curcumin has fewer side effects than drugs currently used for HIPEC. Additionally, although curcumin possesses antitumor effects on various cancers including colon, its efficacy is hindered by a low systemic bioavailability. For HIPEC, curcumin could be delivered directly into the peritoneal cavity, thereby increasing bioavailability. We hypothesize that curcumin used alone or in combination with standard regimen mitomycin C treatment in HIPEC will exert antitumor effects superior to the standard regimen HIPEC. To assess this hypothesis, we developed an in vitro model in which colon cancer cell lines (SK-CO-1, COLO205 and SNU-C1) were treated with curcumin (25 µM) or mitomycin C (1 µM) alone or in combination at different exposure times (1, 2 or 3 hours), and then incubated at either 37°C (normothermia) or 42 °C (hyperthermia), simulating conditions used in clinical practice. Cell lines were chosen in order to determine the effects of p53 (SNU-C1 & COLO205), KRAS (SK-CO-1) and BRAF (COLO205) mutation status on this proposed intraperitoneal chemotherapy strategy. After treatment, cells were maintained at 37°C for 24, 48, and 72 hours after which cell viability was assessed using Annexin V/PI, trypan blue and Hoffman microscopy. Our results indicate that hyperthermia enhances the efficacy of curcumin treatment as evidenced by a significant two-fold decrease in cell viability compared to normothermia in vitro in all three cell lines. No mutation-associated effect was quantified. Though additional comparisons are still forthcoming, the addition of curcumin to HIPEC may be a promising novel therapeutic option. Citation Format: Janviere Kabagwira, Paul A. Vallejos, Audrey H. Choi, Chase Sugiono, Vola-Masoandro Andrianarijaona, Jazmine Chism, William HR Langridge, Maheswari Senthil, Nathan R. Wall. Hyperthermic conditions improve curcumin efficacy for the treatment of peritoneal carcinomatosis of colon cancer origin [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1451.