Costunolide isolated from Vladimiria�souliei inhibits the proliferation and induces the apoptosis of HepG2 cells

Abstract

Costunolide (cos) is one of the major sesquiterpenes isolated from the ethyl acetate soluble fraction of the roots of Vladimiria souliei. In order to explore the effects and molecular mechanism of cos, the anti-proliferative and apoptotic effects of cos against the human hepatoblastoma HepG2 cell line was examined in vitro in the current study. Cell viability was measured using an MTT assay, and IC 50 values (indicating the concentration required to achieve half-maximal inhibition) were calculated to detect the inhibitory effect of cos on HepG2 cell growth. Cell morphology was subsequently observed under an inverted microscope, and cell cycle distribution and apoptosis were detected using flow cytometric analysis. In addition, changes in the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspases-3, -8 and -9 were detected by western blotting. The results of cell analyses indicated that cos treatment inhibited the proliferation and promoted the apoptosis of HepG2 cells in vitro. Cos markedly induced HepG2 cell apoptosis by arresting the cell cycle at the G 2 /M phase in a dose-dependent manner. In terms of the underlying mechanism, cos was revealed to inhibit the anti-apoptotic capacity of the cells, possibly via upregulating the expression levels of Bax protein and caspases-3, -8 and -9, and downregulating the expression of Bcl-2 protein. Taken together, the results of the present study indicate that cos may be a promising candidate for liver cancer therapy, and have provided an insight into the mechanism of action involved in its anti-cancer properties.

Costunolide induces mitochondria-mediated apoptosis in human gastric adenocarcinoma BGC-823 cells

“…Reactive oxygen species (ROS) production induced by costunolide may be the important intermediate link of mitochondrial apoptosis. Costunolide has the potential to activate extrinsic pathway or endoplasmic reticulum stress pathway [21][22][23]. Our research group will be further to explore the mechanisms of costunolide via signaling pathway (such as p53, NF-κB and Wnt/β-catenin signaling pathway) and even find the specific molecular target [6,7].…”

Costunolide-Induced Apoptosis via Promoting the Reactive Oxygen Species and Inhibiting AKT/GSK3β Pathway and Activating Autophagy in Gastric Cancer

“…Many anti-cancer drugs inhibit tumor cell proliferation via stalling the cell cycle ( Wu et al, 2020 ). Cos was found to induce G1/S phase arrest in human esophageal carcinoma Eca-109 cells ( Hua et al, 2016b ) and induce G2/M phase arrest in human liver cancer HepG2 cells and breast cancer MDA-MB-231 cells ( Mao et al, 2019 ). Our study revealed Cos could significantly induce GC cell cycle arrest in the G2/M phase via mediated Cyclin B1, Cdc25c, and Cdk1 protein expression.…”

“…Accumulating evidence has demonstrated multiple pharmacological activities of Cos, including anti-inflammatory, anti-allergic, and anti-microbial effects ( Duraipandiyan et al, 2012 ; Park et al, 2016 ; Lee et al, 2018 ). Recent studies have found that Cos possesses anti-cancer effects against human gastric adenocarcinoma, prostate cancer, liver cancer, bladder cancer, and esophageal cancer, and promotes apoptosis of a variety of cancer cells ( Rasul et al, 2013 ; Hua et al, 2016a ; Chen et al, 2017 ; Mao et al, 2019 ; Yan et al, 2019 ). However, the molecular mechanism underlying the effects of Cos against gastric cancer cells has yet to be elucidated.…”

Incaspitolide A isolated from Carpesium cernuum L. inhibits the growth of prostate cancer cells and induces apoptosis via regulation of the PI3K/Akt/xIAP pathway

“…A BCA protein assay was used to determine the protein concentration, and 10% SDS-PAGE was used to resolve protein samples (50 µg). The proteins were transferred to PVDF membranes, after which blocking, and incubation with the primary and secondary antibodies was performed as described by Mao et al (28). The following primary and secondary antibodies were used: p-PI3K (1:1,000), PI3K (1:1,000), p-Akt (1:1,000), Akt (1:1,000), cleaved-PARP (1:1,000), PARP (1:1,000), xIAP (1:1,000), CDK2 (1:1,000), P53 (1:1,000), CCNA2 (1:1,000), Caspase-3 (1:1,000), GAPDH (1:1,000) and goat anti-rabbit antibody (1:1,000).…”