Tropical lichen, Dirinaria consimilis, induces ROS-mediated activation of MAPKs and triggers caspase cascade mediated apoptosis in brain and cervical cancer cells

Abstract

Lichens are the symbiotic association between photobiont algae and mycobiont fungi having diverse phytochemicals. However, they are still an underexplored natural resource for biological activities. In the present report, we have evaluated the anti-brain and anti-cervical cancer activity of tropical lichen, Dirinaria consimilis (DCME) through the cell viability assay, cell cycle analysis, annexin V-FLUOS staining, morphological analysis, ROS-induction mechanism, evaluation of antioxidant levels, and western blotting study. The WST-1-based cell viability assay showed the cytotoxic nature of DCME towards U87 (IC50-52.65 ± 1.04 µg/ml) and HeLa (IC50-77.60 ± 2.23 µg/ml) cells. Interestingly, DCME does not showed any toxicity towards non-malignant fibroblast cell line WI-38 (IC50-685.80 ± 19.51 µg/ml). Furthermore, the cell cycle analysis showed sub-G1 arrest (apoptosis), and annexin V-FLUOS staining showed an increase in early apoptosis population dose-dependently. Confocal-based morphological data confirmed the DNA condensation and fragmentation upon treatment. Furthermore, DCME treatment induces ROS and regulates the levels of antioxidant enzymes (SOD, Catalase, GST, and GSH) in both U87 and HeLa cells. Finally, the western blotting data revealed the increase in Bax/Bcl-2 ratio, activation of Bid, Caspase-8, -9 and -3 along with degradation of PARP. Moreover, regulation of MAP kinases and activation of p53 was also observed upon DCME treatment. Herein, we first reported the anticancer activity of D. consimilis against brain and cervical cancer cells. Performed in-depth anticancer study revealed the ROS-mediated regulation of MAP kinases and activation of caspase cascade in U87 and HeLa cells upon DCME treatment.

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Acknowledgements

AKS is grateful to the Council of Scientific and Industrial Research (CSIR) Govt. of India for providing the fellowship.

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Correspondence to Nripendranath Mandal.

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AKS, SP, and NM declared no conflict of interest.

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Shendge, A.K., Panja, S. & Mandal, N. Tropical lichen, Dirinaria consimilis, induces ROS-mediated activation of MAPKs and triggers caspase cascade mediated apoptosis in brain and cervical cancer cells. Mol Cell Biochem (2021). https://doi.org/10.1007/s11010-021-04087-4

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Keywords

  • Anticancer
  • ROS
  • Antioxidant enzymes
  • Caspase cascade pathway
  • MAP kinases
  • p53