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The metabolite 5-methyl-1,3-benzenediol and its derivative methyl-2,4-dihydroxy-6-methylbenzoate from the lichen Parmotrema tinctorum with potent apoptotic and anti-angiogenesis effects

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Abstract

Nature has been a rich resource of novel anticancer agents, one such source being lichens, which represent the symbiosis between algae and fungi with diverse range of secondary metabolites having therapeutic significance. With respect to this, the present study evaluates the in vitro apoptogenic profile of secondary metabolites from the lichen Parmotrema tinctorum towards cancer cell lines. Treatment with TLC-purified fraction 1 from P. tinctorum resulted in significant reduction in the cell viabilities of cancer cells with IC50 values ranging between 1.2 and 12.8 μg/ml. The potential anticancer effect of the bioactive fraction was further supported by Trypan blue cell viability, LDH and DNA fragmentation assays. At the cellular level, induction of apoptosis was confirmed through the activation of the caspase cascade and apoptotic cells accumulating in the Sub-G1 phase of cell cycle. Angiogenesis being one of the major characteristics needed for cancer growth, the ability of the lichen fraction to inhibit angiogenesis was checked through in ovo Yolk Sac Membrane (YSM) assay and was found to be significant. The study also verified the non-toxic nature of the bioactive fraction towards normal human peripheral lymphocytes. HPLC analysis and GC–MS characterisation of the bioactive fraction indicated the presence of 5-methyl-1,3-benzenediol and its derivative methyl-2,4-dihydroxy-6-methylbenzoate.

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Availability of data and materials

The data that support the findings of this study are available from the corresponding author (Ashrini Bhaktavalsala Suresh), upon reasonable request.

Code availability [Research Resource Identifiers (RRID)]

HeLa Cell Line RRID: CVCL_0030; HepG2 Cell Line RRID: CVCL_0027; Mcf-7 Cell Line RRID: CVCL_0031; K562 Cell Line RRID: CVCL_0004; ImageJ Software: RRID:SCR_003070; GraphPad Prism Software: RRID:SCR_002798.

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Acknowledgements

The authors thank JAIN (Deemed-to-be-University), Bengaluru for providing the infrastructural support and the Junior Research Fellowship (Ashrini Bhaktavalsala Suresh) to carry out the work. The authors sincerely thank Dr. Roshni Khare, Scientist, Agharkar Research Institute, Pune, India for identifying the lichen in the present study. The authors would also like to thank Dr. M.A. Joseph, Scientist at Central Silk Technological Research Institute, Bengaluru, for providing GC–MS facility and assisting in the analysis of the HPLC fraction.

Accession Number

Parmotrema tinctorum (Despr. ex Nyl.) Hale 19.07 (AMH).

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Not applicable.

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Authors

Contributions

Conceptualization: VKN and ABS; methodology: VKN and ABS; formal analysis and investigation: ABS; writing—original draft preparation: ABS; writing—review and editing: VKN and ABS; supervision: VKN.

Corresponding author

Correspondence to Ashrini Bhaktavalsala Suresh.

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The authors declare that they have no conflict of interest.

Informed consent

The written consent for blood sampling from human volunteers was collected and documented.

Research involving human participants

The blood sampling for lymphocyte isolation from human volunteers was performed as per the ethical guidelines outlaid by ICMR.

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Bhaktavalsala Suresh, A., Kilingar Nadumane, V. The metabolite 5-methyl-1,3-benzenediol and its derivative methyl-2,4-dihydroxy-6-methylbenzoate from the lichen Parmotrema tinctorum with potent apoptotic and anti-angiogenesis effects. 3 Biotech 11, 346 (2021). https://doi.org/10.1007/s13205-021-02883-9

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  • DOI: https://doi.org/10.1007/s13205-021-02883-9

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