Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces cell cycle arrest and apoptosis via the downregulation of Akt in human lung cancer cells

Abstract

The anticancer properties of MHY-449, a novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, in various human cancer cell lines have been previously reported. The aim of the present study was to investigate the activities of MHY-449 on human lung cancer cells in order to elucidate its underlying molecular mechanisms of action. The result showed that MHY-449 treatment inhibited cell growth in a time- and concentration‑dependent manner. Specifically, MHY-449 induced cell cycle arrest at the S phase, and the resulting increased sub-G1 fraction led to the induction of apoptosis, as determined by flow cytometric analysis and DNA fragmentation. In addition, MHY-449 was shown to induce alterations in the ratio of Bax/Bcl-2 protein expression, and contribute to the loss of mitochondrial membrane potential. These cellular events then triggered the caspase cascade and subsequent poly(ADP‑ribose) polymerase cleavage. The apoptotic cell death induced by MHY-449 was inhibited by pretreatment with Z-VAD‑FMK, a pan-caspase inhibitor. Moreover, MHY-449 downregulated the phosphorylation of Akt, and the phosphatidylinositol-3 kinase/Akt inhibitor LY294002 was found to enhance its induction of apoptosis. Taken together, the results suggested that MHY-449 exerts anticancer effects by promoting cell cycle arrest and apoptosis via the downregulation of Akt. Based on these data, MHY-449 serves as a potential candidate in the chemoprevention and/or treatment of lung cancer.

Xanthomicrol Activity in Cancer HeLa Cells: Comparison with Other Natural Methoxylated Flavones

“…Moreover, a significant accumulation of the tsFT210 cells at the G2/M phase was also observed after treatment for 17 h with ART [ 35 ]. Moreover, the increase in the percentage of XAN-treated cancer HeLa cells at the sub-G1 phase, compared to controls, was diagnostic of an increased number of apoptotic cells (sub-G1 population), as previously reported [ 36 ].…”

Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways

“…Cyt-c can activate the caspase cascade after mitochondrial release, inducing the expression of the effector protein caspase-3, and activating cleavage of PARP protein to induce mitochondria-dependent apoptosis. The dynamic balance of Bcl-2/Bax also affects the occurrence of apoptosis [18]. In our study, cytisine caused an increase in expression levels of Cyt-c, BAD, cleaved caspase-3, and PARP protein and a decrease in Bcl-2 protein levels ( Figure 2D).…”

Therapeutic role of meloxicam targeting secretory clusterin-mediated invasion in hepatocellular carcinoma cells

“…The AKT pathway has been considered to exert a crucial role in regulating cell growth, proliferation, survival, and motility ( 25 – 28 ). Our previous studies also revealed that sCLU suppressed HCC cell apoptosis induced by AKT inhibition ( 19 ).…”