Induction of Apoptosis in Lung Cancer Cells by Viburnum grandiflorum via Mitochondrial Pathway

Abstract

Departmental sources Background:Lung cancer is one of the leading causes of mortality and morbidity. Viburnum grandiflorum is a medicinal herb known for its wide spectrum of pharmacological activities, but its anti-cancer properties against lung cancer cells have not been previously investigated. The present study elucidated the antitumor effect and associated mechanism of methanol extract of Viburnum grandiflorum extract (VGE) against lung cancer cells. Material/Methods:The viability of H1650, HCC827, and H1299 cells was measured using MTT assay. Apoptosis and cell cycle progression were determined by flow cytometry using annexin-V/PI and JC-1 stains, respectively. The Lipofectamine Plus reagent (Invitrogen) was used for transfection of caspase-9 plasmid to H1650 and H1299 cells. Results:The results showed decreased H1650, HCC827, and H1299 cell viability by VGE, which occurred in a concentration-and time-dependent manner. The VGE treatment significantly increased the rate of apoptosis in H1650 (P<0.05) and H1299 (P<0.02) cells at 48 and 72 h. Treatment of H1650 and H1299 cells with 10 µM of VGE significantly enhanced the number of cells in sub-G1 phase. The VGE treatment cleaved pro-caspase-8/-9 and-3 in H1650 and HCC827 cells at 72 h. The VGE treatment of H1650 and HCC827 cells reduced Mcl-1 protein expression. Treatment of H1650 and HCC827 cells with VGE markedly decreased the level of p-Akt. However, dominant-negative caspase-9 (caspase-9 dN) plasmid transfection prevented the viability-inhibitory effect of VGE on H1650 and HCC827 cells. Treatment of H1650 and HCC827 cells with VGE increased levels of cytochrome c in the cytosol. Conclusions:VGE inhibited lung carcinoma cell viability by apoptosis activation through a caspase-dependent pathway. Therefore, VGE is a potent anti-cancer agent against lung cancer cells.

Evaluation of Viburnum opulus L. Fruit Phenolics Cytoprotective Potential on Insulinoma MIN6 Cells Relevant for Diabetes Mellitus and Obesity

“…Taking into account the composition of studied extract, it was shown that chlorogenic acid, the main identified phenolic constituent, and its microbial metabolites induced S-phase cell-cycle arrest and activated caspase-3 at 500-1000 µM concentrations in Caco-2 cells [29]. Recently, it was demonstrated that methanolic extract from V. grandiflorum induced apoptosis in lung cancer H1650 and H1299 cell lines [8]. The study revealed the molecular mechanism involved MMP loss, release of cytochrome c into the cytosol, reduction of the anti-apoptotic Mcl-1 protein level, and activation of caspase-3.…”

“…Whereas the antioxidant potential of guelder rose constituents is well characterized, its biological activity on the cellular model is not known very well. There are few studies revealing its anticancer properties against different cell lines, yet they match cytotoxicity with down-regulation of the cellular antioxidant defense system, mitochondria collapse, and cellular death induction [4,[8][9][10][11][12]. Furthermore, even less data indicate the cytoprotective activity of V. opulus, especially in regard to diet-related chronic diseases generated by increased oxidative stress [13,14].…”

Apoptotic Effect of Gallic Acid via Regulation of p-p38 and ER Stress in PANC-1 and MIA PaCa-2 Cells Pancreatic Cancer Cells

“…Inflow cytometric analyses that only employ propidium iodide (PI) labeling, apoptotic cells typically exhibit hypodiploidy [31]. Notably, a biological investigation demonstrates that anticancer activity effectively suppresses the growth of various cancer cells by producing a subG1 population and promoting apoptosis [32][33][34][35][36][37][38][39]. The reduced DNA content observed in sub-G0/G1 cells can be attributed, in part, to the depletion of fragmented chromatin, which is widely recognized as a characteristic feature of apoptosis [40].…”

A Network Pharmacology Approach to Investigate the Anticancer Mechanism and Potential Active Ingredients of Rheum palmatum L. Against Lung Cancer via Induction of Apoptosis

“…Therefore, inhibiting the proliferation and inducing apoptosis of lung cancer has become a feasible strategy for the treatment of lung cancer. A large number of studies have also found that mechanisms of many natural anticancer drugs against lung cancer are related to the regulation of different signaling pathways to inhibit the proliferation of lung cancer cells and induce the apoptosis of lung cancer cells ( Wang S. et al., 2019 ; Han et al., 2020 ; Hu et al., 2020 ). Therefore, we subsequently designed corresponding in vitro experiments in order to prove the prediction results of network pharmacology.…”