Mechanistic Insight into the Autophagic and Apoptotic Activity of Kaempferol on Liver Cancer Cells

Nidhi Sharma,1 Meenakshi Gupta,1 Pragya Anand,2 Yusuf Akhter,2 Noura Al-Dayan,3 Hind Abdul Majed,4 Subhrajit Biswas,5 Sher Ali,6 Maryam Sarwat1 1Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, 201301, India; 2Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, India; 3Department of Medical Laboratory, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia; 4Department of Clinical Microbiology and Immunology, King Abdulaziz University, Jeddah, Saudi Arabia; 5Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh, 201301, India; 6VC Office, Era University, Lucknow, Uttar Pradesh, 226003, IndiaCorrespondence: Maryam Sarwat, Amity Institute of Pharmacy, Amity University, Sector 125, Noida, Uttar Pradesh, 201301, India, Tel +91-9990373875, Email msarwat@amity.edu; maryam21_7@yahoo.comBackground: The accumulation of poorly folded protein in the endoplasmic reticulum (ER) promotes ER stress and contributes to the pathogenesis of hepatocellular carcinoma (HCC). Current therapies have various adverse effects, therefore, laying the need for an alternative approach. Kaempferol (KP), a naturally occurring flavonoid, possesses potent anti-proliferative properties against various cancer cells. Nevertheless, its involvement in HCC remains relatively unexplored, particularly regarding its influence on apoptosis and autophagy pathways.Methods: The effect of KP on cell viability, and motility of Hep3B cells was evaluated by MTT, and scratch assay, respectively. Hoechst staining and FACS analysis were done to check the effect of KP on apoptosis and cell cycle progression. qRTPCR was used to evaluate the expression of several apoptosis and autophagy-related genes. KP was docked with several ER stress-related proteins involved in HCC to gain further insights into molecular mechanisms. The results of docking studies were validated with MD simulation and in vitro studies.Results: Treatment