Antitumor and apoptotic effects of 5-methoxypsoralen in U87MG human glioma cells and its effect on cell cycle, autophagy and PI3K/Akt signaling pathway

Abstract

IntroductionThe main purpose of the current study was to investigate the antitumor effects of 5-methoxypsoralen in U87MG human glioma cells along with studying its effects on cell cycle progression, autophagy and the PI3K/Akt signaling pathway.Material and methodsThe cytotoxic effects of the drug were demonstrated by the MTS cell viability assay while its effects on cellular morphology associated with cell apoptosis were evaluated by phase contrast and fluorescence microscopic techniques. Effects of 5-methoxypsoralen on the cell cycle were studied by flow cytometry while effects on PI3K/Akt proteins were evaluated by western blot assay.ResultsThe results indicate that 5-methoxypsoralen led to time-dependent as well as dose-dependent inhibitory effects on U-87MG human glioma cells. 5-Methoxypsoralen led to a substantial decrease of cell count along with distorted cell morphology. The molecule also led to DNA ladder formation which increased with increasing doses of 5-methoxypsoralen. 5-methoxypsoralen also led to dose-dependent G2/M phase cell cycle arrest. 5-Methoxypsoralen-treated cells also exhibited altered cell ultrastructure with the appearance of autophagic vacuoles and the number of these vacuoles increased with increasing drug dose.ConclusionsIn brief, the results indicate that 5-methoxypsoralen exerted potent anticancer and apoptotic effects in U-87MG human glioma cells along with inducing cell cycle arrest, autophagy and m-TOR/PI3K/Akt signaling pathway inhibition.

A Review on Anti-Tumor Mechanisms of Coumarins

“…In addition, Ferraroni (10) synthesized a series of Coumarins and corresponding 2-thioxocoumarines and tested their inhibitory activities to human carbonic anhydrase CA I, CA II, CA IX, and CA XII, and found that 7-[(1-Phenyl-1H-1,2,3-triazol-4-yl) methoxy]-2H-chromen-2-one (15) and 7-[(1-phenyl-1H-1,2,3triazol-4-yl)methoxy]-2H-chromene-2-thione (16) was the most effective and the selective inhibitors of CA IX and CA XII, with the Kis are comparable to or slightly lower than the standard sulfonamide AAZ. To explore the inhibitory mechanism of 2thioxocoumarin to CA, Ferraroni (10) examined the X-ray crystal structure of 6-hydroxy-2-thioxocoumarin which bound to CA II and found that the inhibitory mechanism of 2-thioxocoumarin is quite different from other coumarins, which work as zinc binders or occlusion of the active site entrance, anchor to the metal-ioncoordinated water/hydroxide ion, or bind to outside of the active sites, then hydrolyzed by CA, finally form the corresponding 2hydroxycinnamic acid derivatives.…”

“…5-methoxypsoralen, also known as bergamot and parsley alkali, is a natural product of furocoumarins and usually isolated from psoralen. Guo (16) found that 5-methoxypsoralen inhibits the expression and phosphorylation of PI3K, Akt, and mTOR in human glioma cells, thereby completely down-regulating the expression and activation of the PI3K/Akt/mTOR signaling pathway. 5-methoxypsoralen can also cause DNA damage by fragment the DNA of human glioma cells, and induce the appearance of autophagy vacuoles.…”

Therapeutic effect of YSY01 on osteoarthritis in rabbit: involvement of suppressing signaling pathway of NF-kB and MMP-9

“…Therefore, chondrocyte clusters can induce calcification in the cartilage matrix a well as the growth and proliferation of chondrocytes, and the activity of chondrocyte clusters is associated with the death of chondrocytes and the generation of apoptotic bodies [4,5]. Moreover, apoptosis is also an important index for the treatment of various diseases via different durgs [6][7][8][9][10]. For example, etanercept could protect ovarian reserve against ischemia-reperfusion injury (IRI) via regulating apoptosis [7], eriodictyol exerted its anticancer activity through induction of mitochondrial apoptosis in the treatment of lung cancer [8], and salvianolic acid A had a synergistically protective effect on hepatic IRI via hepatocellular apoptosis.…”

“…For example, etanercept could protect ovarian reserve against ischemia-reperfusion injury (IRI) via regulating apoptosis [7], eriodictyol exerted its anticancer activity through induction of mitochondrial apoptosis in the treatment of lung cancer [8], and salvianolic acid A had a synergistically protective effect on hepatic IRI via hepatocellular apoptosis. Moreover, 5methoxypsoralen could exert apoptotic effects in U-87MG human glioma cells [9] and glucose fluctuation could also increase mesangial cell apoptosis [10].…”

Anti-tumor effects of isoliquiritigenin in Bcl-2/Bax and PCNA expression of T24 human bladder cancer cells

“…T24 cells exhibit typical morphology of apoptosis after treatment with ISL, including nuclear shrinkage, nuclear fragmentation, chromosome edge set, etc. It is speculated that the anti-tumor mechanism of ISL might be associated with the increase of CDK2 viability, the down-regulation of inner mitochondrial membrane potential (DeltaPsim), and activation of the caspase-3/9-mediated mitochondrial apoptotic signaling pathway [15][16][17][18], but the specific molecular mechanism of ISL in cancer treatment remains unclear.…”