A Tropical Lichen, Dirinaria consimilis Selectively Induces Apoptosis in MCF-7 Cells through the Regulation of p53 and Caspase-Cascade Pathway

Author(s):

Anil K. Shendge, Sourav Panja, Tapasree Basu and Nripendranath Mandal*   Pages 1173 - 1187 ( 15 )

Abstract:

<P>Background: Breast cancer is the most leading cause of death, with 49.9% of crude incidence rate and 12.9% of crude mortality rate. Natural resources have been extensively used throughout history for better and safer treatment against various diseases. </P><P> Objectives: The present study was aimed to investigate the antioxidant and anticancer potential of a tropical lichen Dirinaria consimilis (DCME) and its phytochemical analysis. </P><P> Methods: The DCME was preliminarily evaluated for ROS, and RNS scavenging potential. Furthermore, DCME was evaluated for in vitro anticancer activity through cell proliferation assay, cell cycle analysis, annexin V/PI staining, morphological analysis, and western blotting study. Finally, the HPLC and LC-MS analyses were done to identify probable bioactive compounds. </P><P> Results: The in vitro antioxidant studies showed promising ROS, and RNS scavenging potential of DCME. Moreover, the in vitro antiproliferative study bared the cytotoxic nature of DCME towards MCF-7 (IC50 - 98.58 ± 6.82μg/mL) and non-toxic towards WI-38 (IC50 - 685.85 ± 19.51μg/mL). Furthermore, the flow-cytometric analysis revealed the increase in sub G1 population as well as early apoptotic populations dose-dependently. The results from confocal microscopy showed the DNA fragmentation in MCF-7 upon DCME treatment. Finally, the western blotting study revealed the induction of tumor suppressor protein, p53, which results in increasing the Bax/Bcl-2 ratio and activation of caspase-cascade pathways. </P><P> Conclusion: The activation of caspase-3, -8, -9 and PARP degradation led us to conclude that DCME induces apoptosis in MCF-7 through both intrinsic and extrinsic mechanisms. The LC-MS analysis showed the presence of various bioactive compounds.</P>

Keywords:

Lichen, Dirinaria consimilis, antioxidant, anticancer, p53, caspase-cascade.

Affiliation:

Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme-VIIM, Kolkata-700054, West Bengal, Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme-VIIM, Kolkata-700054, West Bengal, Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme-VIIM, Kolkata-700054, West Bengal, Division of Molecular Medicine, Bose Institute, P-1/12 CIT Scheme-VIIM, Kolkata-700054, West Bengal

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