Molecular authentication, metabolite profiling and in silico-in vitro cytotoxicity screening of endophytic Penicillium ramusculum from Withania somnifera for breast cancer therapeutics.

Autor: Varghese S; School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala 686560 India., Jisha MS; School of Biosciences, Mahatma Gandhi University, Kottayam, Kerala 686560 India.; National Institute of Plant Science Technology (NIPST), Mahatma Gandhi University, Kottayam, Kerala 686560 India.; School of Food Science and Technology, Mahatma Gandhi University, Kottayam, Kerala 686560 India., Rajeshkumar KC; National Fungal Culture Collection of India (NFCCI), Biodiversity and Palaeobiology (Fungi) Gr., Agharkar Research Institute, G.G. Agharkar Road, Pune, 411 004 Maharashtra India., Gajbhiye V; Nanobioscience Group, Agharkar Research Institute, G.G. Agharkar Road, Pune, Maharashtra 411004 India., Haldar N; Nanobioscience Group, Agharkar Research Institute, G.G. Agharkar Road, Pune, Maharashtra 411004 India., Shaikh A; Nanobioscience Group, Agharkar Research Institute, G.G. Agharkar Road, Pune, Maharashtra 411004 India.
Jazyk: angličtina
Zdroj: 3 Biotech [3 Biotech] 2024 Mar; Vol. 14 (3), pp. 64. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1007/s13205-023-03906-3
Abstrakt: In the present study, we isolated a potent endophytic fungus from the roots of Withania somnifera . The endophytic fungal strain was authenticated as Penicillium ramusculum SVWS3 based on morphological and molecular sequencing using four gene data and phylogenetic analyses. In vitro cytotoxicity studies unveiled the remarkable cytotoxic potential of the crude extract derived from P. ramusculum , exhibiting dose-dependent effects on MDA-MB-468 and MCF-7 cells. At a concentration of 100 µg/mL, the crude extract resulted in cell viability of 29.78% for MDA-MB-468 cells and 14.61% for MCF-7 cells. The IC 50 values were calculated as 62.83 ± 0.93 µg/mL and 17.23 ± 1.43 µg/mL, respectively for MDA-MB-468 and MCF-7 cells. Caspase activation assay established the underlying mechanism of the crude extract depicting the activation of caspases 3 and 7, indicating the induction of apoptosis in MCF-7 cells. Chemotaxonomic profiling elucidated the ability of P. ramusculum to synthesize a diverse array of bioactive compounds, including Fasoracetam, Tryprostatin B, Odorinol, Thyronine, Brevianamide F, Proglumide, Perlolyrine, Tyrphostin B48, Baptifoline, etc. Molecular docking studies inferred that Baptifoline, Brevianamide F, Odorinol, Perlolyrine, Thyronine, Tryphostin B48, and Tryprostatin B were the lead compounds that could effectively interact with the five selected target receptors of breast cancer, further surpassing the positive controls analyzed. Pharmacokinetic profiling revealed that Baptifoline, Odorinol, and Thyronine depicted an excellent therapeutic profile of druggability. These findings collectively substantiate the anticancer activity of bioactive metabolites synthesized by P. ramusculum SVWS3. Hence, the endophytic  P. ramusculum  SVWS3 can be an authentic source for developing novel chemotherapeutic drug formulations.
Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03906-3.
Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article.
(© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)
Databáze: MEDLINE
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