Cytotoxic Potential of Alternaria tenuissima AUMC14342 Mycoendophyte Extract: A Study Combined with LC-MS/MS Metabolic Profiling and Molecular Docking Simulation.

Autor: Al Mousa AA; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia., Abouelela ME; Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, P.O. Box 71524, Assiut 11651, Egypt.; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY 40506, USA., Hassane AMA; Botany and Microbiology Department, Faculty of Science, Al-Azhar University, P.O. Box 71524, Assiut 11651, Egypt., Al-Khattaf FS; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia., Hatamleh AA; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia., Alabdulhadi HS; Research Assistant Internship Program, Vice Rectorate for Graduate Studies and Scientific Research, King Saud University, Deanship of Scientific Research, Riyadh 4545, Saudi Arabia., Dahmash ND; Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box 145111, Riyadh 4545, Saudi Arabia., Abo-Dahab NF; Botany and Microbiology Department, Faculty of Science, Al-Azhar University, P.O. Box 71524, Assiut 11651, Egypt.
Jazyk: angličtina
Zdroj: Current issues in molecular biology [Curr Issues Mol Biol] 2022 Oct 20; Vol. 44 (10), pp. 5067-5085. Date of Electronic Publication: 2022 Oct 20.
DOI: 10.3390/cimb44100344
Abstrakt: Breast, cervical, and ovarian cancers are among the most serious cancers and the main causes of mortality in females worldwide, necessitating urgent efforts to find newer sources of safe anticancer drugs. The present study aimed to evaluate the anticancer potency of mycoendophytic Alternaria tenuissima AUMC14342 ethyl acetate extract on HeLa (cervical cancer), SKOV-3 (ovarian cancer), and MCF-7 (breast adenocarcinoma) cell lines. The extract showed potent effect on MCF-7 cells with an IC50 value of 55.53 μg/mL. Cell cycle distribution analysis of treated MCF-7 cells revealed a cell cycle arrest at the S phase with a significant increase in the cell population (25.53%). When compared to control cells, no significant signs of necrotic or apoptotic cell death were observed. LC-MS/MS analysis of Alternaria tenuissima extract afforded the identification of 20 secondary metabolites, including 7-dehydrobrefeldin A, which exhibited the highest interaction score (-8.0156 kcal/mol) in molecular docking analysis against human aromatase. Regarding ADME pharmacokinetics and drug-likeness properties, 7-dehydrobrefeldin A, 4'-epialtenuene, and atransfusarin had good GIT absorption and water solubility without any violation of drug-likeness rules. These findings support the anticancer activity of bioactive metabolites derived from endophytic fungi and provide drug scaffolds and substitute sources for the future development of safe chemotherapy.
Databáze: MEDLINE