Abstract
Although Musca domestica larvae lectin (MLL) is able to inhibit cancer cell proliferation and to induce cancer cell apoptosis, the molecular mechanism(s) responsible for these processes remain elusive. In the current study, the signaling network underlying the MLL-induced apoptosis of human hepatoma BEL-7402 cell was investigated. Our data found out that MLL causes a sustained increase of the intracellular Ca2+ and this process was prevented by the intracellular calcium chelator, BAPTA-AM, suggesting the involvement of intracellular Ca2+ in MLL-induced cell apoptosis. MLL also causes the production of reactive oxygen species and elevates the phosphorylation status of JNK, processes associated with the increased cytoplasmic Ca2+. The mitochondrial permeability transition pore (MPTP) opening study showed that MLL treatment of BEL-7402 cells results in the opening of MPTP and a reduction of mitochondrial transmembrane potential. In such condition, cytochrome-c was detected to be released from mitochondria to cytoplasm through the MPTP. This eventually activates caspase-3 and thus results in apoptosis of the tested BEL-7402 cells. According to a comprehensive review of all the evidence, it is concluded that MLL induces apoptosis of BEL-7402 cells through a Ca2+/JNK-mediated MPTP pathway.
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Acknowledgments
This study was supported jointly by Grants from the Key Projects in the National Science & Technology Pillar Program during the 12th Five-Year Plan Period (2012BAD33B04), the National Natural Science Foundation of China (31000768), and the National High Tech Research Plan (863) (2007AA10Z319).
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Wang, CL., Xia, Y., Nie, JZ. et al. Musca Domestica Larva Lectin Induces Apoptosis in BEL-7402 Cells Through a Ca2+/JNK-mediated Mitochondrial Pathway. Cell Biochem Biophys 66, 319–329 (2013). https://doi.org/10.1007/s12013-012-9489-0
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DOI: https://doi.org/10.1007/s12013-012-9489-0