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Year : 2016  |  Volume : 1  |  Issue : 1  |  Page : 14-19

Anti-leukemic activity of betulinic acid from bulk to self-assembled structure

1 Department of Human Physiology with Community Health, Immunology and Microbiology Laboratory, Vidyasagar University, Midnapore, India
2 Department of Life Science and Biotechnology, Jadavpur University, Kolkata, West Bengal, India

Correspondence Address:
Somenath Roy
Department of Human Physiology with Community Health, Immunology and Microbiology Laboratory, Vidyasagar University, Midnapore - 721 102, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2456-1975.183269

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The Ziziphus jujuba tree is one of the major sources of betulinic acid (BA). After isolation, the bulk structure of the compound was converted to a self-assembled nanofibers (SA-BA) configuration which showed better anti-leukemic efficacy than its bulk form. After internalization in leukemic cells, SA-BA elevated reactive oxygen species (ROS) and pro-inflammatory cytokine secretion which ultimately activated apoptosis pathway. The SA-BA showed potent ameliorative role against acute chemotherapeutic toxicity induced by doxorubicin in human peripheral blood lymphocytes through the mechanism totally opposite to said pathway. Thus, SA-BA showed cell specific distinct effects. It was also revealed that the SA-BA had potent immunomodulatory affected on T cells and macrophages by polarizing the cytokine balance toward Th1 at a slightly higher dose. SA-BA arrested the growth of in vivo cancer by increasing the CD4 + cells in associated with increased cytotoxic T-cell response. SA-BA was also selectively internalized in folate receptor overexpressing leukemic cells. For this purpose, folic acid (FA) and polyethylene glycol (PEG) were conjugated on the nanostructured of SA-BA. After internalization, the conjugate (FA-PEG-SA-BA) diminished the cellular redox system and generated an excess amount of ROS which induced tumor necrosis factor-alpha-mediated cell death through activation of caspase 8 and 3 cascade system. Throughout all these studies, no toxic effects of the conjugates toward normal cells were observed. Thus, the whole study enlightens the multifunctional role of SA-BA in different aspects of anti-leukemic therapy which may be useful in future treatment policies.

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