Ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through inhibition of STAT3 and activation of caspase-3/9

Abstract

Osteosarcoma is composed of tumor osteoblasts and bone-like tissues, with malignant tumors originating from osteogenesis organization. Osteosarcoma is a primary malignant bone tumor. Invasion and metastasis of osteosarcoma affect the prognosis of patients. However, effective therapeutic treatments remain to be identified. The aim of the present study was to investigate the possible inhibitory and apoptotic effects of ginkgetin in osteosarcoma cells. 3.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were used to determine the effect ginkgetin exerted on the growth of osteosarcoma cells. Flow cytometry was used to determine cell apoptosis. STAT3 protein expression and activation of caspase-3/9 were measured using western blot analysis and the MTT and LDH assays, respectively. The results showed that ginkgetin inhibited cell growth and induced cell cytotoxicity in osteosarcoma cells in a dose-dependent manner. Treatment with ginkgetin significantly activated the apoptosis of osteosarcoma cells in a concentration-dependent manner. The anticancer activity of ginkgetin significantly inhibited STAT3 and promoted caspase-3/9 activation in osteosarcoma cells. The findings demonstrated that ginkgetin exerts growth inhibitory and apoptotic effects on osteosarcoma cells through the inhibition of STAT3 and activation of caspase-3/9.

Ginkgetin induces autophagic cell death through p62/SQSTM1-mediated autolysosome formation and redox setting in non-small cell lung cancer

“…Ginkgetin, derived from G. biloba leaves (<0.02% by dry weight) [ 49 ], has been shown to have anti-cancer activity in prostate cancer cells at micromolar concentrations [ 50 ]. In renal cell carcinoma and osteosarcoma, ginkgetin induced cell apoptosis through JAK2/STAT3 signaling [ 51 , 52 ]. We have screened several potential targets for ginkgetin, including Beclin1 and ATG7, and p62 is believed to be the most functional target ( Supplementary Figure 8 ).…”

The WT1/MVP-Mediated Stabilization on mTOR/AKT Axis Enhances the Effects of Cisplatin in Non-small Cell Lung Cancer by a Reformulated Yu Ping Feng San Herbal Preparation

“…Quercetin, kaempferol, isorhamnetin, ginkgolide and bilobalide are the most studied constituents within Ginkgo Folium for cancer therapy. Indeed, ginkgetin, a bioflavonoid in Ginkgo Folium, has been shown to have anti-cancer activity in prostate cancer ( You et al, 2013 ), renal carcinoma ( Ren et al, 2016 ) and osteosarcoma ( Xiong et al, 2016 ). Moreover, the treatment of ginkgetin in lung cancer cells bearing mice could markedly reduce the tumor size, and which was proposed to be mediated by an autophagy-mediated cell death ( Lou et al, 2017 ).…”

ABT-737 potentiates cisplatin-induced apoptosis in human osteosarcoma cells via the mitochondrial apoptotic pathway

“…Mitochondrial-mediated apoptosis has two signaling pathways for programmed cell death: the death receptor pathway and the mitochondrial pathway, which are regulated via caspase-9 and caspase-8, respectively (23). Previous research has shown that caspases play significant roles in the apoptotic cascade (24,25). In the mitochondrial (intrinsic) pathway, members of the Bcl-2 family can regulate apoptosis downstream of caspase protein activation.…”