Document Type
Article
Publication Date
2011
College/Unit
School of Medicine
Department/Program/Center
Medicine
Abstract
As the defining feature of Acute Myeloid Leukemia (AML) is a maturation arrest, a highly desirable therapeutic strategy is to induce leukemic cell maturation. This therapeutic strategy has the potential of avoiding the significant side effects that occur with the traditional AML therapeutics. We identified a natural compound securinine, as a leukemia differentiation-inducing agent. Securinine is a plant-derived alkaloid that has previously been used clinically as a therapeutic for primarily neurological related diseases. Securinine induces monocytic differentiation of a wide range of myeloid leukemia cell lines as well as primary leukemic patient samples. Securinine's clinical potential for AML can be seen from its ability to induce significant growth arrest in cell lines and patient samples as well as its activity in significantly impairing the growth of AML tumors in nude mice. In addition, securinine can synergize with currently employed agents such as ATRA and decitabine to induce differentiation. This study has revealed securinine induces differentiation through the activation of DNA damage signaling. Securinine is a promising new monocytic differentiation inducing agent for AML that has seen previous clinical use for non-related disorders.
Digital Commons Citation
Gupta, Kalpana; Chakrabarti, Amitabha; Rana, Sonia; Ramdeo, Ritu; Roth, Bryan L.; Agarwal, Munna L.; Tse, William; Agarwal, Mukesh K.; and Wald, David N., "Securinine, a Myeloid Differentiation Agent with Therapeutic Potential for AML" (2011). Faculty & Staff Scholarship. 2753.
https://researchrepository.wvu.edu/faculty_publications/2753
Source Citation
Gupta K, Chakrabarti A, Rana S, Ramdeo R, Roth BL, Agarwal ML, et al. (2011) Securinine, a Myeloid Differentiation Agent with Therapeutic Potential for AML. PLoS ONE 6(6): e21203. https://doi.org/10.1371/journal.pone.0021203
Comments
© 2011 Gupta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.