T11TS repress Glioma Mediated Apoptosis in Hematopoietic Stem Cells by Controlling both Extrinsic and Intrinsic Cascade of Cell Death and also rescue from Granzyme B Regulated Gliomagenic Killing
Somnath Mondal,
PhD Fellow,
Calcutta School of Tropical Medicine
Combating gliomagenic global immunosuppression is one of the emerging key for improving prognosis in malignant glioma. Apoptosis plays a pivotal role within the adult hematopoietic system particularly in regulating the cells of immune system. In the present study, we investigated the impact of glioma on apoptotic signalling cascades of bone marrow hematopoietic stems (BMHSCs) and consequences following membrane glycopeptides T11 target structure (T11TS) therapy. Bone marrow smear and Annexin V staining confirm gliomagenic acceleration of apoptotic fate of BMHSCs whereas T11TS treatment in glioma-bearing rats disrupted apoptosis of BMHSCs. Flowcytometry, immunoblotting, and immunofluorescence imagining results revealed multi potent T11TS not only significantly downregulates gliomagenic overexpression of Fas, Fas L, Bid, and caspase-8, the pro-apoptotic extrinsic mediators but also strongly inhibits cytosolic release of cytochrome-c, Apf-1, and Bax to deactivate gliomagenic caspase-9, 3 the key intrinsic apoptotic mediators followed by up modulation of anti-apoptotic Bcl-2 in glioma associated HSCs. T11TS is also able to diminish the perforin-granzyme B mediated apoptotic verdict of BMHSCs during gliomagenesis. The anti-apoptotic action of T11TS on glioma associated BMHSCs provide a crucial insight into how T11TS exerts its immunomodulatory action against glioma mediated immune devastation.
|
|
