Antimetabolic Agent 3-Bromopyruvate Exerts Myelopotentiating Action in a Murine Host Bearing a Progressively Growing Ascitic Thymoma

ABSTRACT

Tumor growth and its chemotherapeutic regimens manifest myelosuppression, which is one of the possible causes underlying the limited success of immunotherapeutic anticancer strategies. Hence, approaches are being designed to develop safer therapeutic regimens that may have minimal damaging action on the process of myelopoiesis. 3-Bromopyruvate (3-BP) is a highly potent antimetabolic agent displaying a broad spectrum antineoplastic activity. However, 3-BP has not been investigated for its effect on the process of myelopoiesis in a tumor-bearing host. Hence, in this investigation, we studied the myelopoietic effect of in vivo administration of 3-BP to a murine host bearing a progressively growing ascitic thymoma designated as Dalton’s lymphoma (DL). 3-BP administration to the DL-bearing mice resulted in a myelopotentiating action, reflected by an elevated count of bone marrow cells (BMC) accompanied by augmented proliferative ability and a declined induction of apoptosis. The BMC of 3-BP-administered mice displayed enhanced responsiveness to macrophage colony-stimulating factor for colony-forming ability of myeloid lineage along with an enhanced differentiation of F4/80⁺ bone marrow-derived macrophages (BMDM). BMDM differentiated from the BMC of 3-BP-administered DL-bearing mice showed an augmented response to lipopolysaccharide and interferon-γ for activation, displaying an augmented tumor cytotoxicity, expression of cytokines, reactive oxygen species, nitric oxide, CD11c, TLR-4, and HSP70. These features are indicative of the differentiation of M1 subtype of macrophages. Thus, this study demonstrates the myelopotentiating action of 3-BP, indicating its hematopoietic safety and potential for reinforcing the differentiation of macrophages in a tumor-bearing host.

KEYWORDS:

• 3-Bromopyruvate
• myelopoiesis
• thymoma
• macrophage differentiation

Acknowledgments

We thankfully acknowledge fellowship support to Saveg Yadav [Award No. 09/013(0577)/2015-EMR-I] from CSIR, New Delhi; Shrish Kumar Pandey [Award No. 3/1/3/JRF-2015(2)HRD]; Yugal Goel [Award No.3/1/3/JRF-2016/LS/HRD-10(80666)] from ICMR, New Delhi; and Mithlesh Kumar Temre [Award No. DBT/JRF/BET-18/I/2018/AL/154] from DBT, New Delhi. Support from DBT, New Delhi, DBT-PURSE ISLS and UGC-UPE, Banaras Hindu University is acknowledged.

Disclosure of interest

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the Council of Scientific and Industrial Research, India [Award No. 09/013(0577)/2015-EMR-I]; Department of Biotechnology, Ministry of Science and Technology [Award No. DBT/JRF/BET-18/I/2018/AL/154]; Indian Council of Medical Research [Award No. 3/1/3/JRF-2015(2)HRD, Award No. 3/1/3/JRF-2016/LS/HRD-10(80666)].