Unveiling the Anti-cancer Potential of Bergenia ciliata (haw.) Sternb: A Mechanistic Study on UPR Modulation and ROS Generation

Abstract Bergenia ciliata (haw.) Sternb, a well-known medicinal plant, has traditionally been used to treat various ailments, such as diabetes, microbial infections, and kidney stones, owing to its anti-inflammatory and anti-tussive properties. Here we aimed to evaluate the anti-cancer potential of the plant extract and deduce the molecular pathways involved. To investigate this, we used the MTT assay to determine the IC50 values of the methanolic extract of B. ciliata (BcME) in MDA-MB-231 and C6-Glioma cell lines. After treating the cancer cell lines with BcME for 18 hours, we evaluated the UPR signalling markers, including pIRE1, Xbp1, ATF6, eIF2α, ATF4, and CHOP, using Immunoblotting. We also used RT-PCR to determine the mRNA levels of ATF4 and performed enzyme assays using Spectrophotometric techniques to measure ROS levels. Our results indicate that B. ciliata has potent anti-cancer properties due to its ability to modulate UPR and ROS pathways. Specifically, the plant extract effectively repressed the cytoprotective UPR by blocking IRE1-Xbp1 and ATF6 pathways while enhancing the PERK-ATF4-CHOP pathway, which is known to switch UPR towards apoptosis. Furthermore, our study revealed that B. ciliata significantly caused the accumulation of ROS in cancer cells and inhibited the antioxidant enzymes catalase and superoxide dismutase. These results conclusively suggest that BcME works synergistically on both UPR and ROS pathways to promote apoptosis and eliminate cancerous cells and thus serves as a potential primary source for bioactive molecules, selectively targeting cancer cells. GRAPHICAL ABSTRACT