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A rohitukine derivative IIIM‐290 induces p53 dependent mitochondrial apoptosis in acute lymphoblastic leukemia cells
Author(s) -
Mintoo Mubashir,
Khan Sameer,
Wani Abubakar,
Malik Sumera,
Bhurta Deendyal,
Bharate Sandip,
Malik Fayaz,
Mondhe Dilip
Publication year - 2021
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23332
Subject(s) - apoptosis , biology , cytochrome c , programmed cell death , leukemia , in vivo , reactive oxygen species , cancer research , mitochondrion , downregulation and upregulation , microbiology and biotechnology , immunology , biochemistry , gene
Abstract Rohitukine, a chromone alkaloid extracted from Dysoxylum binectariferum , has a propitious anticancer activity. Our previous study shows that a new Rohitukine derivative IIIM‐290 restricts the growth of pancreatic cancer in vivo and in vitro . In the present findings, we report the mechanism of cell death induced by IIIM‐290 in MOLT‐4 cells (acute lymphoblastic leukemia) and its anticancer potential against various murine leukemic tumor models in vivo . We found that IIIM‐290 induced apoptosis through upregulation of different apoptotic proteins like PUMA, BAX, cytochrome c, cleaved (active) caspase‐3, and cleaved PARP in MOLT‐4 cells. Moreover, IIIM‐290 abated mitochondrial membrane potential, elevated calcium levels, reactive oxygen species, and arrested growth of MOLT‐4 cells in the synthesis (S) phase of the cell cycle. Interestingly, the elevation in proapoptotic markers was p53 dependent—the silencing of p53 abrogated apoptosis (programmed cell death) triggered by IIIM‐290 in MOLT‐4 cells. Furthermore, IIIM‐290 significantly enhanced the survival of animals with P388 and L1210 leukemia. Thus, our results put IIIM‐290 as a potential candidate for the anticancer lead.