Abstract 4640: Andrographolide modulates cell cycle, cell migration and tumor growth in prostate cancer

Abstract

Abstract Prostate cancer is the most frequently diagnosed non-cutaneous cancer and is the second leading cause of cancer death in American men. Chemopreventive strategies have been tested to prevent the development of different types of cancer including prostate cancer. Andrographolide, a labdane diterpenoid that is the main bioactive component of the medicinal plant Andrographis paniculata, has been reported to have a wide range of biological activities including anticarcinogenic properties. In this study we aim to determine the role of Andrographolide in the progression of prostate cancer using in vitro and in vivo models. Andrographolide significantly inhibited PC3 cell growth at a concentration of 10μM after 24 h of treatment (P < 0.001), and inhibited LNCaP cell growth at a concentration of 15 μM after 24 h of treatment (P < 0.001). Wound healing assays and boyden chamber experiments showed that PC3 prostate cancer cells treated with Andrographolide (25uM) significantly reduced (P<0.001) their migration and invasion. Flow cytometry assays for Annexin V, cell cycle and cell count and viability were performed. Andrographolide (25uM) significantly increased apoptosis, decreased cell population in G1 phase, and reduced count and viability of PC3 cells treated for 48 hours. Immunofluorescence analysis showed that MMP-11 expression levels were significantly decreased and ZO-1 expression was significantly increased in PC3 cells treated with Andrographolide (25uM). Tumor progression was evaluated using a xenograft model in which the anterior prostate lobes of SCID mice were injected with 250,000 22RV1 cells or 500,000 PC3 cells. Andrographolide was administered bi-weekly at concentrations of 10uM and 25uM intraperitoneal injections during 4 weeks (22RV1) or 8 weeks (PC3). Tumor tissue was collected for gross examination, immunohistochemical analysis and gene expression analysis. In vivo results demonstrated that Andrographolide treatment significantly decreased tumor volume when compared with tumors generated in mice treated with vehicle. Our results suggest that the anti-migration and anti-invasion effects of andrographolide may be associated with alterations in the expression of ZO-1 and MMP-11. Citation Format: Ingrid Forestier-Roman, Maria Sánchez, Joseph Casillas, Krizia Rohena, Magaly Martínez-Ferrer. Andrographolide modulates cell cycle, cell migration and tumor growth in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4640. doi:10.1158/1538-7445.AM2015-4640