Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiation.
Ashwagandha (Withania somnifera) is widely used in the Indian traditional system of medicine, Ayurveda. Although it is claimed to have a large variety of health-promoting effects, including therapeutic effects on stress and disease, the mechanisms of action have not yet been determined. In the present study, we aimed to investigate the growth inhibition and differentiation potential of the alcoholic extract of Ashwagandha leaves (i-Extract), its different constituents (Withaferin A, Withanone, Withanolide A) and their combinations on glioma (C6 and YKG1) cell lines. Withaferin A, Withanone, Withanolide A and i-Extract markedly inhibited the proliferation of glioma cells in a dose-dependent manner and changed their morphology toward the astrocytic type. Molecular analysis revealed that the i-Extract and some of its components caused enhanced expression of glial fibrillary acidic protein, change in the immunostaining pattern of mortalin from perinuclear to pancytoplasmic, delay in cell migration, and increased expression of neuronal cell adhesion molecules. The data suggest that the i-Extract and its components have the potential to induce senescence-like growth arrest and differentiation in glioma cells. These assays led us to formulate a unique combination formula of i-Extract components that caused enhanced differentiation of glial cells.
Shah
Navjot
N
National Institute of Advanced Industrial Science and Technology, University if Tsukuba, Ibaraki, Japan.
Kataria
Hardeep
H
Kaul
Sunil C
SC
Ishii
Tetsuro
T
Kaur
Gurcharan
G
Wadhwa
Renu
R
D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004359:Drug Therapy, Combination; D004875:Ergosterol / Q000031:analogs & derivatives / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D014407:Tumor Cells, Cultured; D032341:Withania / Q000737:chemistry*; D054358:Withanolides
C433551:3-rhamnopyranosyl(1-4)-glucopyranosyl-12-diacetoxy-20-hydroxywitha-5,24-dienolide; D010936:Plant Extracts; D054358:Withanolides; C009684:withaferin A; C030693:Ashwagandha; D004875:Ergosterol