Aqueous Ethanolic Extract of Tinospora cordifolia as a Potential Candidate for Differentiation Based Therapy of Glioblastomas

Abstract

Glioblastomas are the most aggressive primary brain tumors and their heterogeneity and complexity often renders them non responsive to various conventional treatments. Search for herbal products having potential anti-cancer activity is an active area of research in the Indian traditional system of medicine i.e., Ayurveda. Tinospora cordifolia, also named as ‘heavenly elixir’ is used in various ayurvedic decoctions as panacea to treat several body ailments. The current study investigated the anti-brain cancer potential of 50% ethanolic extract of Tinospora cordifolia (TCE) using C6 glioma cells. TCE significantly reduced cell proliferation in dose-dependent manner and induced differentiation in C6 glioma cells, resulting in astrocyte-like morphology as indicated by phase contrast images, GFAP expression and process outgrowth data of TCE treated cells which exhibited higher number and longer processes than untreated cells. Reduced proliferation of cells was accompanied by enhanced expression of senescence marker, mortalin and its translocation from perinuclear to pancytoplasmic spaces. Further, TCE showed anti-migratory and anti-invasive potential as depicted by wound scratch assay and reduced expression of plasticity markers NCAM and PSA-NCAM along with MMP-2 and 9. On analysis of the cell cycle and apoptotic markers, TCE treatment was seen to arrest the C6 cells in G0/G1 and G2/M phase, suppressing expression of G1/S phase specific protein cyclin D1 and anti-apoptotic protein Bcl-xL, thus supporting its anti-proliferative and apoptosis inducing potential. Present study provides the first evidence for the presence of anti-proliferative, differentiation-inducing and anti-migratory/anti-metastatic potential of TCE in glioma cells and possible signaling pathways involved in its mode of action. Our primary data suggests that TCE and its active components may prove to be promising phytotherapeutic interventions in gliobalstoma multiformae.

Tinospora cordifolia inhibits autoimmune arthritis by regulating key immune mediators of inflammation and bone damage

“…Chemical standardization, nature of bioactive components, and toxicity of TCE are described previously by other investigators. [14][15][16][17] Several bioactive phytochemical constituents belonging to the sub-categories of alkaloids (e.g., berberine, tinosporin), glycosides (e.g., cordiofolioside A, palmatosides C), sesquiterpenoids (e.g., tinocordifolin), diterpenoid lactones (e.g., tinosporon, columbin), aliphatic compounds (e.g., octacosanol), and steroids (e.g., makisterone A, giloinsterone) have been identified in T. cordifolia. [14][15][16][17] …”

Mortalin is Expressed by Astrocytes and Decreased in the Midbrain of Parkinson's Disease Patients

“…In this study, we provide evidence of the presence of mortalin in both primary mouse astrocyte cultures and post-mortem human brain tissue. To date, mortalin has been studied largely in the context of neurons, with only a few reports describing enhanced mortalin expression in gliomas (1,13,18) and not detected in normal astrocytes by immunohistochemistry (18). Here, we used immunofluorescence which may be significantly more sensitive than standard immunohistochemistry techniques.…”

Octacosanol Enhances the Proliferation and Migration of Human Umbilical Vein Endothelial Cells via Activation of the PI3K/Akt and MAPK/Erk Pathways

“…Having been isolated from Tinospora cordifolia (TCE), octacosanol was verified exerting efficient inhibitory effects on proliferation of endothelial cells and growth of ehrlich ascites tumor cells, and was identified as a new antiangiogenic compound suppressing neovascularization induced by angiogenic factors in chick chorioallantoic membrane and rat cornea in vivo angiogenesis assays [12]. Meanwhile, 50 % ethanolic extract of TCE significantly reduced glioma cell proliferation and differentiation in a dose-dependent manner and showed anti-migratory and anti-invasive potential as depicted by wound scratch assay [19]. On the contrary, TCE has been reported to stimulate the growth and proliferation of Human LNCaP cells (which are androgen-sensitive human prostate adenocarcinoma cells) [20].…”