Germacrone inhibits the proliferation of glioma cells by promoting apoptosis and inducing cell cycle arrest

Abstract

Germacrone is one of the major bioactive components of the traditional Chinese Medicinal plant Curcuma aromatica Salisb. and has been shown to possess anti‑tumor properties. In the present study, the anti‑proliferative effect of germacrone on human glioma cells and the molecular mechanism underlying its cytotoxicity were investigated. Treatment of the U87 and U251 human glioma cell lines with germacrone inhibited the cell proliferation in a dose‑ and time‑dependent manner as assessed by MTT assay, while significantly lower effects were observed on normal human astrocytes. Flow cytometric analysis and DNA fragmentation revealed that germacrone promoted apoptosis of glioma cells, associated with an increased expression of p53 and bax and decreased expression of bcl‑2. Furthermore, flow cytometric cell cycle analysis revealed that germacrone induced G1 phase arrest, associated with an obvious decrease in the expression of cyclin D1 and CDK2 and an increased expression of p21. In conclusion, the present study suggested that germacrone may be a novel potent chemopreventive drug candidate for gliomas via regulating the expression of proteins associated with apoptosis and G1 cell cycle arrest.

Germacrone attenuates cerebral ischemia/reperfusion injury in rats via antioxidative and antiapoptotic mechanisms

“…Liu et al observed that GM‐induced apoptosis in HepG2 cells via suppression of the JAK2/STAT3 signaling pathway. In another study, it was shown that GM inhibited the proliferation of glioma cells by elevating apoptosis and promoting cell cycle arrest . These two studies show a contrary effect from what we observed.…”

“…11 GM exerted a remarkable protective effect on acute liver injury in mice. 12,13 Liu et al 14 showed that treatment with GM suppressed cell proliferation.…”

Nutritional value, phytochemical composition, and biological activities of edibleCurcumaspecies: A review

“…Biological activities Curcuma aeruginosa Antimicrobial [164] , cytotoxicity [152] ; antinociceptive, antipyretic [13] ; uterine relaxant [74] ; antioxidant [165] ; inhibition of nitric oxide production [166] ; and anti-inflammatory [153] Curcuma amada Antifungal and insecticidal [79] ; CNS depressant and analgesic [16,167] ; antiulcer [168] ; anti-tubercular [135] ; antioxidant, antimicrobial, cytotoxic and antiplatelet [20] ; anti-inflammatory [169] ; anticancer [170] ; and larvicidal [171] Curcuma angustifolia Antimicrobial, antiulcerogenic [172,173] ; antioxidant [155] ; antifungal and antibacterial [129] Curcuma aromatica Hypoglycemic [172] ; anti-Alzheimer [173] ; antioxidant [2] ; cytotoxicity [174] ; insecticidal [175] ; antiinflammatory [169] ; antibacterial [11] ; inhibition of nitric oxide production [176] ; antiproliferative [177] ; and gastroprotective [21] Curcuma australasica Inhibition of nitric oxide and prostaglandin production, anti-inflammatory, and cytotoxic [115] Curcuma caesia Smooth muscle relaxant [178] ; anxiolytic, CNS depressant and neuropharmacological [179,180] ; antimicrobial [151] ; antiulcerogenic [181] ; antitumor and antioxidant [116] ; anticancer [182] ; antihepatotoxicity and nephrotoxicity [...…”

Antiviral Activity of Germacrone against Pseudorabies Virus in Vitro

“…In particular, the germacrone and oseltamivir combination has a synergistic effect on the inhibition of influenza virus. On the other hand, there are no reports on potential antitumor activity in vivo [33]. The main possible reasons for this phenomenon are: (1) germacrone is mainly extracted and isolated from plants with relatively low yield, therefore the purchase price is high, while the dosage for animal experiments is large; (2) the water solubility of germacrone is relatively poor; and (3) the lack of an antitumor and antivirus mechanism.…”