Succinyl rotundic acid inhibits growth and promotes apoptosis in the HeLa cervical cancer cell line

Abstract

Rotundic acid (RA) is a kind of pentacyclic triterpene saponins, which widely exists in holly and other plants. It has anti-tumor and lipid-lowering effects, and has been widely used in the prevention and treatment of vascular diseases. Succinyl RA (SRA) is a kind of circular acid derivative with strong water solubility. However, SRA’s effect and mechanism about the therapy of cervical cancer is still not clarified. The inhibitory effect of SRA on Hela cells and its molecular mechanism were investigated in this study. Hela cell line was used to establish an in vitro model to study the effect of SRA. The effects of SRA on cell proliferation, cell cycle and apoptosis were analyzed by flow cytometry and detected by 3-(4,5-dimethyl thiazole-2-yl)-2, 5-diphenyltetrazole bromide. The experimental results show that SRA can inhibit the growth of Hela and diffusion, inducing cell apoptosis. SRA can also reduce the expression of CyclinD 1 and p21. It was also decreased the expression of apoptosis inhibitor B cell lymphoma (Bcl-2), and increased the expression of Bcl-2-related X-protein and Caspase-3. This study provides evidence for the progress of SRA in inhibiting Hela cells and presents potential applications of SRA as an alternative therapy for cervical cancer.

Synthesis, Characterization, In Vitro Anticancer Potentiality, and Antimicrobial Activities of Novel Peptide–Glycyrrhetinic-Acid-Based Derivatives

“…The Bcl-2 protein introduces a central role in tumor growth or suppression the intrinsic apoptotic pathway [ 49 ]. Conversely, the pro-apoptotic Bax acts essentially to enhance the process of cell apoptosis [ 50 , 51 , 52 , 53 ]. Increasing the level of the anti-apoptotic Bcl-2 within the cancerous cell boosts the cell survival through inhibiting apoptosis [ 50 ].…”

Efficacy of Rotundic Acid and Its Derivatives as Promising Natural Anticancer Triterpenoids: A Literature‐Based Study

“…[46,112] A succinyl derivative of RA (succinyl RA) also induced apoptosis in Hela cell lines at the concentration between 10-40 μmol/L and the compound also diminished the apoptosis inhibitor Bcl-2, and enhanced the expression of Bcl-2related X-protein and caspase-3 which, indicating the potentiality of the compound in the therapy of cervical cancer. [113] Anti-proliferative effect Cancer development and progression are determined by the proliferation of abnormal cells, which is often driven by changes in the expression or activity of cell cycle-related proteins. [114] It is a reliable target for anticancer drug design.…”

“…[118] A recent study demonstrated that the succinyl derivative of RA (Succinyl RA) also inhibits Hela cell proliferation at a concentration of 10-40 μmol/L by reducing the expression of CyclinD1 and p21, indicating the potentiality of the compound in the treatment of cervical cancer. [113] Anti-angiogenic effect…”

“…Various research teams also expressed in their several investigations that several synthetic derivatives of RA also induce apoptosis in different cancerous cells, such as D1 (1.25–100 μM) induced significant apoptotic cell death in HeLa, HepG2 and SGC‐7901 cell lines as well as the compound D4 also manifested apoptosis at the concentration of 10–40 μM by elevating cleaved caspase‐3 and Bax, and diminishing Bcl‐2 expression [46,112] . A succinyl derivative of RA (succinyl RA) also induced apoptosis in Hela cell lines at the concentration between 10–40 μmol/L and the compound also diminished the apoptosis inhibitor Bcl‐2, and enhanced the expression of Bcl‐2‐related X‐protein and caspase‐3 which, indicating the potentiality of the compound in the therapy of cervical cancer [113] …”

“…(2016) also reported in their several studies that RA derivatives (D5–D6) at concentrations of 5–40 μM have an anti‐proliferative effect against A375, and SPC−A1 cells [118] . A recent study demonstrated that the succinyl derivative of RA (Succinyl RA) also inhibits Hela cell proliferation at a concentration of 10–40 μmol/L by reducing the expression of CyclinD1 and p21, indicating the potentiality of the compound in the treatment of cervical cancer [113] …”