Abstract
Glioma causes significant mortality across the world and the most aggressive type of brain cancer. The incidence of glioma is believed to increase in the next few decades and hence more efficient treatment strategies need to be developed for management of glioma. Herein, we examined the anticancer effects of Indirubin against a panel of human glioma cells and attempted to explore the underlying mechanisms. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay showed that Indirubin could inhibit the growth of all the glioma cells but the lowest IC50 of 12.5 µM was observed against the U87 and U118 glioma cells. Additionally, the cytotoxic effects of Indirubin were comparatively negligible against the normal astrocytes with an IC50 of > 100 µM. Investigation of mechanism of action, revealed that Indirubin exerts growth inhibitory effects on the U87 and U118 glioma cells by autophagic and apoptotic cell death. Annexin V/PI staining assay showed that apoptotic cell percentage increased dose dependently. Apoptosis was associated with increase in Bax decrease in Bcl-2 expressions. Additionally, the expression of autophagic proteins such as LC3II, ATG12, ATG15 and Beclin 1 was also increased. Wound heal assay showed that Indirubin caused remarkable decrease in the migration of the U87 and U118 cells indicative of anti-metastatic potential of Indirubin. Taken together, these results suggest that Indirubin exerts potent anticancer effects on glioma cells and may prove essential in the management of glioma.
Highlights
Gliomas include all tumors of glial origin and accounts for about 77% of all the primary tumors of brain (Ohgaki and Kleihues 2005)
Indirubin inhibited the growth of all the glioma cells (Table 1), more profound growth inhibitory effects were observed on the U87 and U118 glioma and cells with IC50 range from 12.5 to 25 μM
The results showed that Indirubin caused apoptosis of the U87 and U118 glioma cells and was accompanied with enhancement of Bax and depletion of Bcl-2 expression
Summary
Gliomas include all tumors of glial origin and accounts for about 77% of all the primary tumors of brain (Ohgaki and Kleihues 2005). Considered to be among the most destructive human cancers, gliomas cause tremendous human mortality throughout the globe (Ostrom et al 2014). Surgery followed by chemo- and radiotherapy is generally employment for the management of gliomas (Malmer et al 2001). Li et al AMB Expr (2020) 10:171 first time report that Indirubin suppresses the proliferation of human glioma cells via induction of apoptosis and autophagy. It suppresses the migration of the human glioma cells. Taken together these results suggest that Indirubin may prove to be beneficial lead molecule for the development of chemotherapy for glioma
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