Abstract 5945: Gnetin C for chemoprevention and chemotherapy of prostate cancer

Abstract

Prostate cancer is common among aging men. No cancer treatment is provided during active surveillance for prostate cancer. Targeted nutritional interception may prove to be the most appropriate chemoprevention for intermediate- and high-risk patients. Here, for the first time, we investigate the efficacy of Gnetin C, a resveratrol-dimer found abundantly in melinjo (Gnetum gnemon) plant that is characterized with improved pharmacokinetics compared to other stilbenes, in a transgenic mouse model of prostate cancer. We have generated two prostate-specific mouse models, one overexpressing MTA1 on the background of Pten heterozygosity (R26MTA1; Pten+/f), and the other overexpressing MTA1 on the background of Pten loss (R26MTA1; Ptenf/f). Chemoprevention design included Gnetin C- dietary supplementation in the high-risk model while the therapeutic design included i.p. administration in the more aggressive R26MTA1; Ptenf/f genotype. Our results show that while MTA1 cooperates with PTEN deficiency to accelerate PIN development by increasing MTA1-associated signaling, Gnetin C intervention combats the progression of prostate cancer. We show that mice treated with Gnetin C (7 mg/kg bw, daily i.p.) exhibited more favorable histopathology with decreased severity and number of PIN foci (41.23% reduction) accompanied by reduced proliferation (Ki67, 57.43% reduction), angiogenesis (CD31, 86.91% reduction), AR (31.57% reduction), and MTA1 (27.94% reduction). Ongoing chemopreventive studies with four different diets [Control-diet; Gnetin C high dose (70 mg/kg diet); Gnetin C low dose (35 mg/kg diet); and pterostilbene (70 mg/kg diet)] are in progress. Altogether, these data provide an evidence for efficacy of Gnetin C in blocking prostate cancer progression and reveal its potential for novel chemopreventive and therapeutic implications in prostate cancer.Supported by NCI/NIH R15CA216070 to ASL Citation Format: Gisella Campanelli, Rabab Al Deabel, Anand Puaar, Prashanth Parupathi, Amee Adhvaryu, Avinash Kumar, Anait S. Levenson. Gnetin C for chemoprevention and chemotherapy of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5945.