Abstract 2343: Andrographolide treatment results in decreased mtDNA damage and loss of the mitochondrial membrane potential while increasing ROS production in prostate cancer
Authors: Roque-Reyes Yarelis M. , Sosa-Rivera Jesus , Sánchez-Vázquez María M. , Ayala-Peña Sylvette , Torres-Ramos Carlos A. , Martínez-Ferrer Magaly 
Published: June 2022

Introduction: Prostate Cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer deaths in men worldwide. Andrographolide, a labdane diterpenoid that is the main bioactive component of the medicinal plant Andrographis paniculata, has shown a wide range of therapeutic potential against many factors including cancer. Previous studies in our laboratory showed that Andrographolide induces expression of DNA repair genes associated with double-strand break repair, cell growth suppression, cell cycle arrest, and apoptosis in PCa in vitro. Andrographolide also showed an altered ATP production ratio between mitochondrial-ATP and glycolysis-ATP production in PC3 and 22RV1 cell lines treated with Andrographolide. However, the mechanism of action of Andrographolide in prostate cancer is not completely known. The objective of this study is to determine the role of Andrographolide in mtDNA damage, mitochondrial ROS production, and mitochondrial membrane potential in prostate cancer cell lines.

Methods: Prostate cancer cell lines (PC3 and 22Rv1) were treated with Andrographolide (25μM) for 24 and 48 hours. DNA isolated from treated and control cells was used to detect mtDNA damage using a PCR-based method. To evaluate ROS production, cells were incubated with MitoSOX and fluorescence detected using fluorescence microscopy. Membrane potential status was also determined with fluorescence microscopy, using the dye JC-1.

Results: Detection of mtDNA damage in PC3 cells treated with Andrographolide for 48 hours and in 22Rv1 cells treated with Andrographolide for 24 and 48 hours, show decreased mtDNA lesions in treated cells. Evaluation of mitochondrial membrane potential shows membrane depolarization in 22Rv1 cells treated with Andrographolide. In addition, mitochondrial ROS production shows a 1.4-fold increase in 22Rv1 cells treated with Andrographolide for 24 hours.

Conclusion: This study shows that Andrographolide disrupts mitochondrial function in PC3 and 22Rv1 PCa cells, which in turn may trigger a metabolic phenotype leading to cell death PCa. This research could provide new insights into the role of Andrographolide in PCa altering bioenergetics and mitochondrial function, making Andrographolide a promising therapeutic candidate as a metabolic modulator and a chemo preventive agent in prostate cancer.

Citation Format: Yarelis M. Roque-Reyes, Jesus Sosa-Rivera, María M. Sánchez-Vázquez, Sylvette Ayala-Peña, Carlos A. Torres-Ramos, Magaly Martínez-Ferrer. Andrographolide treatment results in decreased mtDNA damage and loss of the mitochondrial membrane potential while increasing ROS production in 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 2343.