Rotundic acid induces Cas3‑MCF‑7 cell apoptosis through the p53 pathway

Abstract

In the present study, the functions and mechanisms of rotundic acid (RA) underlying its induction of apoptosis in caspase-3-transfected MCF-7 human breast cancer cells (Cas3-MCF-7 cells) were investigated. RA induced apoptosis in Cas3-MCF-7 cells more efficiently compared with that in MCF-7 cells transfected with control plasmid. The results from an MTT assay demonstrated that RA effectively inhibited Cas3-MCF-7 cell viability in a dose-dependent manner and induced cell apoptosis via caspase-3 activity within 12 to 48 h. Western blotting and fluorescence-activated cell sorting demonstrated that RA initiated Cas3-MCF-7 cell apoptosis via p53 activation. The silencing of the p53 gene in the Cas3-MCF-7 cell line led to decreased RA-induced Cas3-MCF-7 cell caspase-3 activity and cell apoptosis. Collectively, the results of the present study indicate that caspase-3 serves a critical function in rotundic acid-induced apoptosis, and suggest that caspase-3 deficiency may contribute to the chemotherapy-resistance of breast cancer. Reconstitution of caspase-3 sensitizes MCF-7 breast cancer cells to chemotherapy. RA has the potential for development as a novel drug combined with reconstitution of caspase-3 gene therapy for the treatment of human breast cancer with caspase-3 deficiency.

Anti-breast cancer synthetic peptides derived from the Anabas testudineus skin mucus fractions

“…Another experimental result also found that the MCF7 cells are caspase-3 deficient with a partial deletion in the CASP-3 gene; these cells underwent cell death that lacked typical apoptotic properties 53 . However, Nan et al confirmed that caspase-3 serves a critical function in MCF7 cell, and they suggested that caspase-3 deficiency may contribute to the chemotherapy-resistance of breast cancer 38 , 54 .…”

Absolute bioavailability, dose proportionality, and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method

“…Rotundic acid (RA), a plant-derived and ursane-type pentacyclic triterpene acid, was identified as a major active ingredient of IRC and has been shown to exert extensive pharmacological effects, including antimicrobial [ 3 , 4 ], anti-inflammatory [ 5 ], anticancer [ [6] , [7] , [8] , [9] , [10] , [11] , [12] , [13] ], and lipid-decreasing effects [ 14 ]. It has also been proven to alleviate type 2 diabetes and its complications by improving the composition of the gut microbiota [ 15 ].…”

Rotundic Acid Promotes Angiogenesis Potentially by Activating the STAT3 -JAK Signaling Pathway

“…Rotundic acid (RA) belongs to the pentacyclic triterpenoid family and is mainly found in water fly thrips such as Ilex rotundus, which are widely distributed in China Haraguchiet & Xie et al [17,18]. Previous studies reported the anticancer efficacy of RA both in vitro and in vivo Nan & Roy et al [19,20]. However, the effects of RA in treating IHD remain enigmatic.…”