Sotetsuflavone inhibits proliferation and induces apoptosis of A549 cells through ROS-mediated mitochondrial-dependent pathway

Abstract

BackgroundSotetsuflavone is isolated from Cycas revoluta Thunb., which has biological activity against tumors. However, the anti-proliferative effects of sotetsuflavone on A549 cells and its mechanism are not fully elucidated.MethodsThis study investigated the mechanisms of growth inhibition, cell cycle arrest and apoptosis in non-small cell lung cancer A549 cells induced by sotetsuflavone and evaluated whether sotetsuflavone can be safely utilized by humans as therapeutic agent.ResultsWe found that sotetsuflavone had significant antiproliferative activity against A549 cells. At the same time, the reactive oxygen species (ROS) content increased while the mitochondrial membrane potential and the ratio of Bcl-2/Bax decreased. Cleaved caspase-3, cleaved caspase-9, cytochrome C and Bax expression increased, and Cyclin D1, CDK4, cleaved caspase-8 and Bcl-2 expression decreased. Interestingly, we demonstrated that sotetsuflavone could effectively inhibit the G0/G1 cycle progression, and then induce the endogenous apoptosis pathway. Our results show that sotetsuflavone could inhibit the growth of A549 cells by up-regulating intracellular ROS levels and causing the mitochondrial membrane potential to collapse, inducing G0/G1 phase arrest and endogenous apoptosis.ConclusionsIn short, we confirm that sotetsuflavone had an inhibitory effect on A549 cells and discovered that it causes apoptosis of A549 lung cancer cells. Sotetsuflavone may be used as a novel candidate for anti-tumor therapy in patients with lung cancer.

Sotetsuflavone Induces Autophagy in Non-Small Cell Lung Cancer Through Blocking PI3K/Akt/mTOR Signaling Pathway in Vivo and in Vitro

“…Previously, we demonstrated that sotetsuflavone was able to inhibit the migration and invasion, and able to induce apoptosis and cycle arrest of A549 cells (Wang et al, 2018a;Wang et al, 2018b). Thus, we used Cell scratch assays, Transwell invasion assays, Tunel assays, and flow cytometry to test whether or not sotetsuflavone was able to inhibit the migration and invasion, as well as induce apoptosis and cell cycle arrest in H1650 cells.…”

“…In the early stages of analysis, we used the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method to detect the function and effects of sotetsuflavone on the viability of A549 cells. Results indicated that sotetsuflavone had a strong inhibitory effect on the levels of activity of A549 cells (Wang et al, 2018a). To further verify whether or not sotetsuflavone is a potent inhibitor of A549 cell proliferation, we used 5-ethynyl-20-deoxyuridine (EDU) and colony formation experiments.…”

“…We used a MTT cell proliferation and cytotoxicity assay kit to detect the levels and degree of cell viability as previously described (Wang et al, 2018a). For the colony formation assay, cells were seeded at a density of 500 cells/well in 6-well plates and treated with different concentrations of sotetsuflavone.…”

“…Western blotting based detections were performed according to the previous descriptions from Wang et al (2018a). Briefly, we extracted total cell proteins, and then lysed the samples in a RIPA buffer with an added protease inhibitor.…”

Extract of Cycas revoluta Thunb. enhances the inhibitory effect of 5-fluorouracil on gastric cancer cells through the AKT-mTOR pathway

“…is an evergreen palm woody plant[36] with useful medicinal value, such as reducing fever and alleviating congestion. A component of the extract, Sotetsuflavone, was identified to have strong anti-tumor activity against lung cancer cells[37,38]. Because it can effectively induce lung cancer cell apoptosis, we studied whether it could inhibit growth, migration and invasion of malignant gastric cancer cells.…”