Andrographolide induces DNA damage in prostate cancer cells

// Ingrid S. Forestier-Roman 1, 2 , Andres Lopez-Rivas 2, 3 , Maria M. Sanchez-Vazquez 2 , Krizia Rohena-Rivera 1, 2 , Gretchen Nieves-Burgos 2, 3 , Humberto Ortiz-Zuazaga 4 , Carlos A. Torres-Ramos 5 and Magaly Martinez-Ferrer 2, 6 1 Department of Biochemistry, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico, USA 2 University of Puerto Rico Comprehensive Cancer Center, Division of Cancer Biology, San Juan, Puerto Rico, USA 3 Department of Biology, University of Puerto Rico at Rio Piedras, San Juan, Puerto Rico, USA 4 Department of Computer Sciences, University of Puerto Rico at Rio Piedras, San Juan, Puerto Rico, USA 5 Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico, USA 6 Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico, San Juan, Puerto Rico, USA Correspondence to: Magaly Martinez-Ferrer, email: magaly.martinez1@upr.edu Keywords: chemoprevention; phytochemicals; mouse model; DNA repair; gene expression Received: March 28, 2017      Accepted: January 09, 2019      Published: February 01, 2019 ABSTRACT Prostate cancer (PCa) is the most common diagnosed cancer and is the third cause of cancer mortality in men in the USA. Andrographolide, a diterpenoid lactone isolated from Andrographis paniculata, has shown to possess anticarcinogenic activity in a variety of cancer cells. In this study, we examined the efficacy of Andrographolide in PCa using in vitro and in vivo models. Androgen-independent (PC3) and androgen-dependent (22RV1) cell lines were treated with Andrographolide to determine the effect in cell motility, cell proliferation and apoptosis. Andrographolide decreased PCa cell migration, decreased invasion, and increased cell apoptosis in vitro . Tumor growth was evaluated using an orthotopic xenograft model in which the prostates of SCID mice were injected with 22RV1, and mice were treated three times per week with Andrographolide 10 mg/kg. Andrographolide decreased tumor volume, MMP11 expression and blood vessels formation in vivo . Gene expression analysis identified cellular compromise, cell cycle, and “DNA recombination, replication and repair” as the major molecular and cellular functions altered in tumors treated with Andrographolide. Within DNA repair genes we confirmed increased expression of genes involved in DNA double strand break repair. Consistent with this observation we detected increased γH2AX in Andrographolide treated tumors and in cells in culture. Taken together, these data suggest that Andrographolide inhibits PCa by promoting DNA damage.