Evaluation of the Anticancer Activity and Mechanism Studies of Glycyrrhetic Acid Derivatives toward HeLa Cells

Abstract

In this paper, a series of glycyrrhetic acid derivatives 3a–3f were synthesized via the esterification reaction. The cytotoxicity of these compounds against five tumor cells (SGC-7901, BEL-7402, A549, HeLa and B16) and normal LO2 cells was investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The results showed that compound 3a exhibited high antiproliferative activity against HeLa cells (IC50 = 11.4 ± 0.2 μM). The anticancer activity was studied through apoptosis, cloning, and scratching; the levels of the intracellular ROS, GSH, and Ca2+; and the change in the mitochondrial membrane potential, cell cycle arrest and RNA sequencing. Furthermore, the effects of compound 3a on gene expression levels and metabolic pathways in HeLa cells were investigated via transcriptomics. The experimental results showed that this compound can block the cell cycle in the S phase and inhibit cell migration by downregulating Focal adhesion kinase (FAK) expression. Moreover, the compound can reduce the intracellular glutathione (GSH) content, increase the Ca2+ level and the intracellular ROS content, and induce a decrease in the mitochondrial membrane potential, further leading to cell death. In addition, it was also found that the mechanism of compounds inducing apoptosis was related to the regulation of the expression of mitochondria-related proteins B-cell lymphoma-2 (Bcl-2), Bcl-2-Associated X (Bax), and the activation of the caspase proteins. Taken together, this work provides a help for the development of glycyrrhetinic acid compounds as potential anticancer molecules.

Discovery of Novel Pentacyclic Triterpene Acid Amide Derivatives as Excellent Antimicrobial Agents Dependent on Generation of Reactive Oxygen Species

“…It has been reported that pentacyclic triterpenoid derivatives often inhibit the growth of cancer cells and are dependent on ROS activity [ 38 , 39 ]. However, their mechanism of action in the field of pesticides has rarely been reported.…”

Simultaneous inhibition of FAK and ROS1 synergistically repressed triple-negative breast cancer by upregulating p53 signalling

“…In NSCLC cells, FOCAD inhibited FAK activity, enhancing sensitivity to ferroptosis [ 53 ]. Additionally, inhibition of FAK activity in ovarian [ 54 , 55 ] and cervical cancers [ 56 ] led to decreased GSH levels. FAK also serves as a scaffold for the binding of p53 and Mdm2, regulating ferroptosis via p53 [ 57 ].…”

Exploring the Potential of Extracts from Sloanea medusula and S. calva: Formulating Two Skincare Gels with Antioxidant, Sun Protective Factor, and Anti-Candida albicans Activities

“…In general, identified compounds in HPLC-MS analysis have exhibited properties that benefit skin health, such as antimicrobial, antioxidant, anti-inflammatory, chemoprotective, cytotoxic, and wound-healing properties [ 49 , 50 , 51 , 52 ]. Therefore, these compounds may be responsible for the observed biological activities.…”