title: Augmentation of myelopoiesis in a murine host bearing a T cell lymphoma following in vivo administration of proton pump inhibitor pantoprazole.
abstract: Proton pump inhibitors (PPI) are being proposed as potent antitumor agents, owing to their ability to specifically induce tumor cell death by reversing H(+) ion homeostasis. As tumor growth induces myelosuppression in tumor-bearing hosts, it remains unclear if PPI can also modulate tumor-induced myelosuppression. Thus, we studied the effect of in vivo administration of pantoprazole (PPZ), a PPI, on myelopoiesis in a murine model of a transplantable T cell lymphoma, designated as Dalton's lymphoma (DL). Intraperitoneal administration of PPZ to tumor-bearing mice resulted in an enhanced bone marrow cellularity, inhibited induction of apoptosis and augmented bone marrow cell (BMC) survival. BMC of PPZ-administered tumor-bearing mice showed elevated number of F4/80 positive cells, augmented colony forming ability and differentiation in bone marrow-derived macrophages (BMDM) with higher expression of F4/80 and CD11c markers. This study also presents evidences to indicate that PPZ-dependent augmentation of myelopoiesis in the tumor-bearing host is dependent on an enhanced expression of M-CSF and receptors for M-CSF & GM-CSF in BMC, along with a modulation in the expression of cell survival regulatory molecules PUMA, Bcl2, p53 and caspase-activated DNase (CAD). BMDM obtained from PPZ-administered tumor-bearing mice also showed an augmented expression of TLR-2, tumoricidal activity, production of NO and monokines: IL-1, IL-6 & TNF-α. The study discusses the possible mechanisms underlying PPZ-dependent augmentation of myelopoiesis. Taken together, the present study proposes that a PPZ-dependent alleviation of tumor-induced myelosuppression could contribute to an augmented myelopoiesis.
authors: School of Biotechnology, Banaras Hindu University, Varanasi 221 005, UP, India.
authors: Naveen Kumar
authors: NK
authors: Vishvakarma
authors: Sukh Mahendra
authors: SM
authors: Singh
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned; D004797:Enzyme-Linked Immunosorbent Assay; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D038042:Myelopoiesis / Q000187:drug effects*; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D017077:Culture Media, Conditioned; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole