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A core fucose specific lectin from Cephalosporium curvulum induces cellular apoptosis in hepatocellular and pancreatic cancer cells and effective in detecting AFP

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Abstract

Cephalosporium curvulum lectin (CSL), a lectin from pathogenic fungus has exquisite specificity towards α1–6 linkage of core fucosylated glycans, expressed in hepatocellular and pancreatic cancer. Interaction and effect of CSL and other fucose specific lectins LCA and AOL on HepG2 and PANC-1 cells was investigated. CSL, LCA and AOL exhibited strong binding to PANC-1 cells which could be effectively blocked by competing glycoprotein mucin. Effect of CSL, LCA and AOL on PANC-1 and HepG2 cells was determined by MTT assay and all the three lectins inhibited the cell growth which could be blocked by mucin, cell cycle analysis revealed that CSL increased hypodiploid HepG2 cell population indicating cellular apoptosis. CSL induced apoptosis in HepG2 cells was confirmed by Annexin V/PI assay. CSL induced increase in early apoptotic HepG2 cell population, a time dependent increase in the expression of caspases-3, 9 and cytochrome-c was observed by western blotting suggesting the possible involvement of intrinsic caspase dependent apoptosis. Increase in ROS and decrease in MMP demonstrated involvement of intrinsic caspase dependent apoptosis. Quantification of AFP in HCC patients using CSL lectin-antibody sandwich ELISA, supports diagnostic potential of CSL.

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Acknowledgements

Dr. Shashikala Inamdar acknowledges the support by funding from Department of Science and Technology, India (No.SR/S0/BB-0085/2010/ 2012), UGC for the funding from under UPE (F.No14-4/2012(NS/PE) and The Karnatak Cancer Therapy and Research Institute, Padmashree Dr. R. B. Patil Hospital, Hubli, Karnataka for providing serum samples, Shivakumar Belur acknowledges UGC for RGNFSC.

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Belur, S., Jagadeesh, N., Swamy, B.M. et al. A core fucose specific lectin from Cephalosporium curvulum induces cellular apoptosis in hepatocellular and pancreatic cancer cells and effective in detecting AFP. Glycoconj J 37, 435–444 (2020). https://doi.org/10.1007/s10719-020-09921-3

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