Tannic acid inhibits lipid metabolism and induce ROS in prostate cancer cells

Prashanth K B Nagesh,Subhash C Chauhan,Nirnoy Dan,Vivek Kumar Kashyap,Elham Hatami,Shashi Jain,Pallabita Chowdhury,Murali M Yallapu,Meena Jaggi

doi:10.1038/s41598-020-57932-9

Abstract

Prostate cancer (PCa) cells exploit the aberrant lipid signaling and metabolism as their survival advantage. Also, intracellular storage lipids act as fuel for the PCa proliferation. However, few studies were available that addressed the topic of targeting lipid metabolism in PCa. Here, we assessed the tannic acid (TA) lipid-targeting ability and its capability to induce endoplasmic reticulum (ER) stress by reactive oxygen species (ROS) in PCa cells. TA exhibited dual effects by inhibiting lipogenic signaling and suppression of lipid metabolic pathways. The expression of proteins responsible for lipogenesis was down regulated. The membrane permeability and functionality of PCa were severely affected and caused nuclear disorganization during drug exposure. Finally, these consolidated events shifted the cell’s survival balance towards apoptosis. These results suggest that TA distinctly interferes with the lipid signaling and metabolism of PCa cells.

Highlights

Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, 92037, USA. *email: signaling by diminishing the competence of protein-folding mechanisms, resulting the rise of unfolded protein levels[15]
Similar growth inhibitory patterns were observed in invasion and migration studies of xCELLigence system during Tannic acid (TA) treatment of C4-2 and PC-3 cells (Supplementary Fig. 1B,C)
To assess the chemo-sensitive attributes of TA, we investigated the combinatorial implications of TA through Rhodamine 123 (Rh123) dye accumulation studies

Summary

Introduction

Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, 92037, USA. *email: signaling by diminishing the competence of protein-folding mechanisms, resulting the rise of unfolded protein levels[15]. *email: signaling by diminishing the competence of protein-folding mechanisms, resulting the rise of unfolded protein levels[15] These correlations between ER stress and ROS mechanisms can be implicated in therapeutic targeting in cancer cells. The ROS accumulations were due to the declination of ROS scavenging abilities like reduction of enzymatic activity such as superoxide dismutase and glutathione peroxidase[18] This induced ROS considerably affects the liveliness of membrane bilayers and disrupts their integrity. Hydroxyl radical (HO) and hydroperoxyl (HO2) are the most prevalent ROS species that affect the lipids[19] These reactive compounds can affect the permeability and fluidity of membranes consisting of lipid bilayers that remarkably affect cell survival and integrity[20]. In this study, we evaluated TA’s ability in ROS induction and its ability to interfere lipid metabolism as well as disruption of membranes which subsequently destabilizes PCa cellular integrity

Methods

Results

Discussion

Conclusion