Gossypin Induces G2/M Arrest in Human Malignant Glioma U251 Cells by the Activation of Chk1/Cdc25C Pathway

Abstract

Gossypin is a flavone that was originally isolated from Hibiscus vitifolius and has traditionally been used for the treatment of diabetes, jaundice, and inflammation. Recently, gossypin was found to have potent anticancer properties; however, its effect on human gliomas still remain unknown. To investigate the potential anticancer effects of gossypin on malignant gliomas and analyze the associated molecular mechanisms, we treated human glioma U251 cells with gossypin. Our study showed that the treatment of U251 cells with gossypin inhibited cell proliferation in a dose- and time-dependent manner and was observed to be minimally toxic to normal human astrocytes. Gossypin's effect on cell cycle distribution was observed, and we found that it induced G2/M-phase arrest in U251 cells. An analysis of cell-cycle regulatory proteins indicated that the arresting effect of gossypin on the cell cycle at G2/M phase was involved in the phosphorylation of cell division cycle 25C (Cdc25C) tyrosine phosphatase via the activation of checkpoint kinase 1 (Chk1). These findings indicate that gossypin is a potential treatment of gliomas because of gossypin's potential to regulate the proliferation of U251 cells via the cell-cycle regulatory proteins Chk1 and Cdc25C.

Anti-tumor effect of α-pinene on human hepatoma cell lines through inducing G2/M cell cycle arrest

“…p53 also plays a role on the guardian of G2/M check point; p53 activates the transcription of p21 and 14-3-3s (16,17). While p21 directly suppresses activities of CDC2 (18), and interferes with PCNA and CDC25 (19), 14-3-3s binds to CyclinB1 and excludes it from the nucleus (20). Moreover, the dissociation of CDK1-CyclinB1 complexes is also mediated by p53 through inducing Gadd45 (Growth arrest and DNA damage inducible gene) (21,22).…”

Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells

“…Plant extracts with these properties are rich in phenolic compounds such as phenolic acids, flavonoids, flavonol glycosides, anacardic acids, proanthocyanidins, phenylcoumarins, theaflavins, cannabinoids, phenolic amides, curcuminoids, stilbene oligomers, xanthones, phenolic oils and flavonoligans (Anilkumar 2010). Specific phenolic compounds include quercetin (Dajas 2012), anacardic acid (Sun et al 2006;Hsieh & Hernández-Ledesma 2011), epigallocatechin gallate (EGCg) (Khan & Mukhtar 2008), gallic acid (Verma et al 2013), proanthocyanidins (Nandakumar et al 2008), curcumin (Goel et al 2008), cannabinoids (Alexander et al 2009), mangostin (Nakagawa et al 2007;Johnson et al 2012), gossypin (Kim et al 2008;Shi et al 2012), silymarin (Ramasamy & Agarwal 2008), gingerols and shagoals Sang et al 2009). In addition, anticancer effects can also include inhibition of cell growth, cell-cycle arrest, induction of apoptosis, inhibition of topoisomerase enzymes and matrix metalloproteinases as well as angiogenesis.…”

Gossypin: A phytochemical of multispectrum potential

“…From the present study, it was also concluded that gossypin inhibits proliferation of U251 cells through Chk1 and Cdc25C which are cell-cycle regulatory proteins [29]. Anticarcinogenic and antitumor potential of gossypin was evaluated and showed zone of inhibition in topo I and topo II inhibition assay in Saccharomyces ceriviseae mutant cultures.…”