Abstract

Abstract Breast cancer is the most frequent malignant tumor among women and is the leading cause of death from cancer worldwide. In 2020, 90,222 deaths from breast cancer were reported in México. However, cancer cells resistant to antineoplastic drugs are frequent, which compromises the patient’s survival. For this reason, in oncology, it is essential to search for new sources of anticancer compounds. Endophytic fungi are currently considered potential reservoirs for compounds with antitumor activity. More than 100 different classes of secondary metabolites have been reported with activity against different types of cancer, including breast cancer. Therefore, the objective of this study was to evaluate the activity of methanol extracts of endophytic fungi isolated from Lophocereus marginatus against the MCF-7 breast cancer cell line, using as controls the MA-104 cell line human peripheral blood mononuclear cells. Fungal strains were isolated from stems of L. marginatus and molecularly identified from ribosomal DNA internal transcript spacer region sequencing. Extraction of the secondary metabolites was performed from the maceration of mycelium fungus in methanol. The solvent was removed with a rotary evaporator and the extract was reconstituted with dimethyl sulfoxide (DMSO). Next, cells were incubated with the extract at concentrations ranging from 31.25 µg/mL to 250 µg/mL for 48 h at 37 °C and 5% CO2. Growth inhibition was assessed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction assay, using 1% DMSO was used as a negative control. IC50 values and selectivity indexes (SI) were then calculated. It was found that tumor cells growth inhibition by the extracts increased in a concentration-dependent manner. A. versicolor PME-H005 strain extract showed the highest antitumor activity, with up to 58.9% growth inhibition at 250 µg/mL and IC50 value of 95.21 ± 1 µg/mL against MCF-7 cells. The highest SI was obtained with MCF-7 cell s with 2.77, as compared with normal PBMC with an IC50 of 264 ± 1.5 µg/mL. In addition, the M. anisopliae PME-H007 strain presented a high SI value of 2.1 and an IC50 of 245.9 ± 1.9 µg/mL, using the MCF-7 cell line. This study shows the potential of the endophytic fungus A. versicolor PME-H005 isolated from L. marginatus for production of secondary metabolites with antitumor activity against MCF-7 cells. Citation Format: Jesica M. Ramírez Villalobos, Cesar I. Romo Sáenz, Karla S. Morán Santibañez, Patricia Tamez Guerra, Orquídea Pérez González, Reyes Tamez Guerra, Cristina Rodríguez-Padilla, Ricardo A. Gomez Flores. In vitro antitumoral activity of endophytic fungi isolated from Lophocereus marginatus against the human breast cancer cell line MCF-7 [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-27.

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