Prostate cancer is the most frequently diagnosed non-cutaneous cancer and the second cause of cancer-related deaths in American men. Andrographolide, a labdane diterpenoid that is a component of the medicinal plant Andrographis paniculata, has been reported to have a wide range of biological activities including anticarcinogenic properties. In previous studies, we found that Andrographolide inhibits cell growth, tumor growth and angiogenesis in prostate cancer. Therefore, the objective of this study is to determine the mechanism of action of Andrographolide in prostate cancer. In order to determine the mechanism of action, we did gene expression profile to compare genes differentially expressed in tumors treated with Andrographolide (10 mg/kg and 25 mg/kg) and their vehicle. Tumors were developed using a xenograft model in which the prostates of SCID mice were injected with 22RV1, and mice were treated bi-weekly with Andrographolide (10 mg/kg and 25 mg/kg). Tumor tissues were collected and snap frozen. Gene expression was analyzed using the Affymetrix GeneChip® Human Gene 2.0 array. Microarray studies showed a total of 674 genes differentially expressed in tumors treated with Andrographolide (10 mg/kg) when compared to their vehicle. In addition, 218 genes were differentially expressed in tumors treated with Andrographolide (25 mg/kg) when compared to their vehicle. Genes involved in cellular processes such as cell cycle, DNA damage response, MAPK signaling, TCA cycle, glycolysis and metabolism of amino acids were differentially expressed. Ingenuity Pathway Analysis (IPA) revealed networks associated to DNA replication, recombination and repair, and post-translational modification in tumors treated with Andrographolide (10 mg/kg). Moreover, IPA revealed networks associated to cell death and survival, cellular function and maintenance, and carbohydrate metabolism in tumors treated with Andrographolide (25 mg/kg). The microarray results were confirmed by quantitative real-time PCR. Our results demonstrated that Andrographolide altered the expression of genes associated with DNA repair which could be a possible mechanism of action of its anticarcinogenic effect.

Citation Format: Ingrid Forestier-Román, María Sánchez-Vázquez, Krizia Rohena-Rivera, Carmen Cadilla, Magaly Martínez-Ferrer. Andrographolide alters genes associated with DNA repair in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 79.