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.
Highlights
Glioblastomas are the most aggressive and highly invasive primary brain tumor types
Various bioactive components have already been isolated from Tinospora cordifolia which belongs to different classes of compounds such as alkaloids, diterpenoid, lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds and polysaccharides
Several recent studies have reported that various extracts of Tinospora cordifolia plant possess bioactive components which inhibit cellular proliferation in various in vitro models and show antineoplastic [32], antitumor [33,34,35], anti-angiogenesis [36,37] and anti metastatic activity in various in vivo models [35,37,38]
Summary
Glioblastomas are the most aggressive and highly invasive primary brain tumor types. The complexity and highly dynamic nature of multiple oncogenic pathways involved in the survival of these tumor cells renders them nonresponsive to various available radiotherapeutic and chemotherapeutic treatments. Various bioactive components have already been isolated from Tinospora cordifolia which belongs to different classes of compounds such as alkaloids, diterpenoid, lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds and polysaccharides. This plant has been used as remedy for jaundice and its extracts and purified components have been found to have hepatoprotective effect against various toxic agents [3,4]. Apart from this, many previous studies have provided evidence for the presence of adaptogenic [18], cardioprotective [19], antioxidant [20,21] anti-inflammatory [22,23], and antipsychotic [24] activities in this plant. Several recent studies have reported that various extracts of Tinospora cordifolia plant possess bioactive components which inhibit cellular proliferation in various in vitro models and show antineoplastic [32], antitumor [33,34,35], anti-angiogenesis [36,37] and anti metastatic activity in various in vivo models [35,37,38]
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