Euphornin reduces proliferation of human cervical adenocarcinoma HeLa cells through induction of apoptosis and G2/M cell cycle arrest

Abstract

BackgroundThe plant Euphorbia helioscopia L. has been used in traditional Chinese medicine for treating various disorders such as tuberculosis and edema. The aim of this study was to investigate the effect of euphornin, a bioactive compound isolated from E. helioscopia, on proliferation of human cervical adenocarcinoma HeLa cells by analyzing cell viability, rate of apoptosis, and cell cycle progression.Materials and methodsThe sulforhodamine B assay was used to study the effect of euphornin on the proliferation of HeLa cells. Morphological changes to cell nuclei were identified after Hoechst 33342 staining. Mitochondrial membrane depolarization (MMP) was analyzed after staining with JC-1 dye. The influence of euphornin on the apoptosis rate was analyzed by Annexin V/propidium iodide double staining. Fluorescence-activated cell sorting was applied to investigate the influence of euphornin on cell cycle progression. Proteins were obtained from HeLa cells and analyzed by Western blots.ResultsA cell viability assay showed that euphornin inhibited proliferation of HeLa cells in a dose-dependent and time-dependent manner. Euphornin also induced apoptosis in a concentration-dependent manner, with the rates of apoptosis ranging from 25.3% to 52.6%. A high concentration of euphornin was found to block HeLa cells at the G2/M stage. A Western blot analysis suggested that euphornin might exhibit antitumor activity by inducing apoptosis. Euphornin treatment altered the ratio of Bax/Bcl-2 in HeLa cells, which led to the release of cytochrome complex. The levels of cleaved caspase-3, caspase-8, caspase-9, and caspase-10 were also markedly increased by euphornin treatment. Analysis of cell cycles indicated that euphornin induced cell cycle arrest by increasing the level of the phospho-CDK1 (Tyr15) protein. The various assays demonstrated that euphornin treatment resulted in a significant suppression of cell growth accompanied by G2/M cell cycle arrest and increased rate of apoptosis via mitochondrial and caspase pathways.ConclusionOur findings suggest that euphornin has the potential to be used as a cancer therapeutic agent against human cervical adenocarcinoma.

Inhibition of LDHA suppresses cell proliferation and increases mitochondrial apoptosis via the JNK signaling pathway in cervical cancer cells

“…Cervical cancer is the second most common type of cancer and one of the most common types of gynecological malignancy in women worldwide (1-3) with ~500,000 new cases and 270,000 deaths in 2018 (4). In China, the average age range is 30-35 years for onset of cervical cancer and 45-55 years for invasive cancer (5). Investigation of the molecular mechanisms that promote the pathogenesis of cervical cancer is needed.…”

Chemical Composition and Antimicrobial Activity of the Essential Oil From Euphorbia helioscopia L.

“…2 The aerial parts of this plant, referred to as "Ze Qi" in China, are used as traditional medicine for the treatment of ascites, edema, tuberculosis, phlegm, cough, and ringworm. 3,4 The ethanolic extract of this plant has been reported to possess strong antibacterial activity against Pseudomonas aeroginosa and Staphylococcus aureus. 5 The secondary metabolites of E. helioscopia are reported to include terpenoids, amino acids, flavonoids, tannins, and steroids, 6,7 some of which exhibit obvious antimicrobial activity.…”

LC–MS profiling, in vitro and in silico C-ABL kinase inhibitory approach to identify potential anticancer agents from Dalbergia sissoo leaves

“…All the tentatively identified phytochemicals were previously reported from various sources other than Dalbergia sissoo and have the potential to inhibit cancer cell growth or be used as anticancer agents (Table S2 ) 39 , 48 , 53 – 62 . The pharmacological activity of the extracts depends upon the presence of phytochemicals and the amount of those phytochemicals.…”