Synthesis of novel pentacyclic triterpenoid derivatives that induce apoptosis in cancer cells through a ROS-dependent, mitochondrial-mediated pathway - Sorbonne Université Access content directly
Journal Articles (Review Article) Molecular Pharmaceutics Year : 2022

Synthesis of novel pentacyclic triterpenoid derivatives that induce apoptosis in cancer cells through a ROS-dependent, mitochondrial-mediated pathway

Abstract

Betulinic acid (BA) and oleanolic acid (OA) are plant-derived conjugates found in various medicinal plants that have emerged as potential antitumor agents. Herein, a series of novel BA and OA derivatives were synthesized by conjugation with per-O-methylated-β-cyclodextrin (PM-β-CD), and their anticancer properties against a panel of three human cancer cell lines were evaluated. Two OA-PM-β-CD conjugates (48 and 50) were observed to be the most potent conjugates against the three cell lines (MCF-7, BGC-823, and HL-60), with a 15- to 20-fold decrease in the IC50 values (IC50: 6.06–8.47 μM) compared with their parental conjugate (OA). Annexin V-FITC/propidium iodide staining and Western blot analysis revealed that both conjugates induced apoptosis in HL-60 cells. Additionally, in the representative conjugate 48-treated HL-60 cells, a decrease in mitochondrial membrane potential and subsequent release of cytochrome c into the cytosol were observed, indicating the activation of the intrinsic apoptosis pathway. Furthermore, 48 dramatically induced the generation of reactive oxygen species (ROS) in HL-60 cells, and the corresponding effect could be reversed using the ROS scavenger N-acetylcysteine. Collectively, these results suggest that the novel pentacyclic triterpenoid derivatives trigger the intrinsic apoptotic pathways via the ROS-mediated activation of caspase-3 signaling, inducing cell death in human cancer cells.
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Dates and versions

hal-03980531 , version 1 (09-02-2023)

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Boyang Cheng, Xindang Chu, Ruiwen Liu, Xinyuan Ma, Mengyang Wang, et al.. Synthesis of novel pentacyclic triterpenoid derivatives that induce apoptosis in cancer cells through a ROS-dependent, mitochondrial-mediated pathway. Molecular Pharmaceutics, 2022, 20 (1), pp.701-710. ⟨10.1021/acs.molpharmaceut.2c00885⟩. ⟨hal-03980531⟩
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