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Updated: Apr 16, 2026
Deciphering the Molecular Mechanism and Function of Pore-Forming Toxins Using Leishmania major
Published on: October 28, 2022
Lipid from infective L. donovani regulates acute myeloid cell growth via mitochondria dependent MAPK pathway
Nabanita Chatterjee1, Subhadip Das1, Dipayan Bose1
1Cancer Biology & Inflammatory Disorder Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata-700032, West Bengal, India.
Abstract:
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.
Insights
Leishmanial lipid (pLLD) from L. donovani effectively inhibits acute myeloid leukemia (AML) cell growth. This lipid induces apoptosis and cell cycle arrest, offering a potential new therapeutic strategy for AML.
Area of Science:
- Microbiology
- Cell Biology
- Oncology
Background:
- Microbial components are increasingly significant for therapeutic interventions.
- Leukemia, particularly acute myeloid leukemia (AML), remains a challenging disease to treat.
Purpose of the Study:
- To investigate the anti-neoplastic potential of leishmanial lipid (pLLD) from L. donovani against acute myeloid leukemia cells.
- To explore the mechanisms by which pLLD affects AML cell growth and survival.
Main Methods:
- Treatment of four AML cell lines (HL-60, MOLT-4, U937, K562) with pLLD.
- Analysis of cell proliferation, apoptosis (morphological changes, Annexin V staining, DNA fragmentation), cell cycle, intracellular ROS, mitochondrial membrane potential, and protein expression (Bax, Bcl2, Bad, t-Bid, PARP, ERK1/2, JNK1/2, p38, caspases 9/3).
Main Results:
- pLLD significantly inhibited proliferation in all tested AML cell lines.
- pLLD induced apoptosis and G0/G1 cell cycle arrest in U937 cells.
- pLLD increased intracellular ROS, altered mitochondrial membrane potential, and modulated apoptosis-related protein expression.
- pLLD activated MAPK signaling pathway (ERK1/2, JNK1/2, p38) and caspases 9/3.
Conclusions:
- Leishmanial lipid (pLLD) exhibits significant anti-neoplastic activity against acute myeloid leukemia cells.
- pLLD induces apoptosis through ROS generation, mitochondrial dysfunction, and modulation of key apoptotic proteins.
- pLLD's mechanism involves cell cycle arrest and activation of MAPK and caspase pathways, suggesting its therapeutic potential for AML.
