Piceatannol May Slow Cancer Cachexia‐Induced Weight‐Loss In Vivo

Abstract

Cancer‐associated cachexia (CAC) is the ongoing loss of lean muscle and adipose that results in functional impairment. CAC reduces chemotherapy effectiveness, lowers quality of life, and is considered the direct cause of death in up to 20% of all cancer mortalities. Strategies that preserve body weight can improve survival and quality of life. Recent reports indicate that preserving adipose mass, specifically, is a key strategy to protect body weight and increase survival in CAC. Piceatannol is resveratrol analog with anti‐inflammatory and anti‐adipogenic properties. We recently demonstrated that piceatannol, unlike resveratrol, inhibits lipolysis, the main mechanism of adipose loss in CAC, in cancer‐associated conditions in vitro. In this study, we evaluated piceatannol's effect in tumor‐induced weight loss. Five‐week‐old female BALB/c mice were inoculated with C26 colon carcinoma cells, an established model of CAC wasting. Following tumor establishment, mice received daily piceatannol injection for two weeks. Piceatannol treatment showed a strong trend in protecting against tumor‐induced weight loss and wasting. The effect of piceatannol appeared to be independent of tumor growth, as no difference in tumor size and volume was detected between piceatannol‐treated and vehicle‐treated tumor‐bearing mice. In addition, mice receiving piceatannol treatment exhibited higher serum triglycerides than vehicle‐treated tumor‐bearing mice. Dual‐energy X‐ray absorptiometry revealed a trend for preserved lean muscle in piceatannol‐treated mice with little effect on fat mass. This study lays the foundation for the use of piceatannol, a natural small‐molecule, in the preservation of body weight in CAC.Support or Funding InformationNIH, 5R03CA184544‐01A1 and U.S. Department of Agriculture National Needs Fellowship