Andrographolide alters metabolism and mitochondrial function in prostate cancer

Prostate cancer (PCa) is the second most common diagnosed cancer and the fifth cause of cancer mortality in men worldwide. In the United States, PCa is the most common diagnosed cancer and the third cause of cancer mortality in men. PCa is often treated using radiation, chemotherapy or radical prostatectomy. However, the combination of natural products with the standard of care treatment is an emerging area of cancer therapeutics. Previous studies from our laboratory showed that Andrographolide inhibits prostate cancer progression through a DNA damage response mechanism. In this study, we investigated the role of Andrographolide in metabolic function. Tumor development was performed by using an orthotopic xenograft model in which the prostates of SCID mice were injected with the prostate cancer cell line 22RV1. These mice were treated three times per week with Andrographolide 10 or 25 mg/kg for 4 weeks. Tumor tissue was collected to evaluate the effect of Andrographolide in tumor gene expression. Microarray analysis identified carbohydrate metabolism, connective tissue development and function, and cell cycle as a major molecular and cellular function altered in tumors treated with Andrographolide. Specifically, we found that the expression profiles of SASS6, FBXL4, MYDGF, TKK, MRSP33 and ZNF766 were significantly altered, suggesting that Andrographolide may be altering tumor metabolism. To confirm this observation, bioenergetics profile was determined using an Extracellular Flux Analyzer (Seahorse XF Mito Stress assay). The results of these experiments indicate that Andrographolide treatment decreases the Maximum and Spare Respiratory Capacity of PCa cells. These data suggest that Andrographolide disrupts the bioenergetics profile of PCa cells. Support or Funding Information Work funded by Institutional funds from the University of Puerto Rico Comprehensive Cancer Center and the School of Pharmacy. HOZ was supported in part by NIH‐NCI grant U54CA096297. MARC grant 5T34GM007821‐38. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .