Lipid from infective L. donovani regulates acute myeloid cell growth via mitochondria dependent MAPK pathway.
The microbial source, which includes live, attenuated, or genetically modified microbes or their cellular component(s) or metabolites, has gained increasing significance for therapeutic intervention against several pathophysiological conditions of disease including leukemia, which remains an incurable disease till now despite recent advances in the medical sciences. We therefore took up the present study to explore if the leishmanial lipid (pLLD) isolated from L. donovani can play an anti-neoplastic role in acute myeloid leukemia cells by regulating cellular growth. Indeed pLLD significantly inhibited cell proliferation of four AML cell lines (HL-60, MOLT-4, U937, and K562). Scanning electron microscopy and DNA fragmentation analysis revealed that it significantly induced apoptosis of U937 cells through morphological alteration. Occurrence of apoptosis was checked by using Annexin exposure and this established that the cell cycle was arrested at G0/G1 phase in time-dependent manner. pLLD increased the intracellular ROS with alteration of mitochondrial membrane potential, as detected using DCFDA. It also regulated the expression of apoptosis-related proteins like Bax, Bcl2, Bad and t-Bid besides causing cleavage of PARP as determined by western blot analysis. Treatment of U937 cells with pLLD induced the activation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK)1/2, p38, and caspases 9/3. The results suggest that pLLD induces apoptosis in acute myeloid leukemia cells possibly via increasing intracellular ROS and regulating the MAPK pathway.
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, West Bengal, India.
Nabanita
N
Chatterjee
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, West Bengal, India.
Subhadip
S
Das
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, West Bengal, India.
Dipayan
D
Bose
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, West Bengal, India.
Somenath
S
Banerjee
Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, P. O. Box 17020, Jadavpur University, Kolkata 700032, India.
Tarun
T
Jha
Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, West Bengal, India.
Krishna
K
Das Saha
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D006801:Humans; D007893:Leishmania donovani / Q000737:chemistry*; D008055:Lipids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D008055:Lipids; D017382:Reactive Oxygen Species