Fungi are an excellent source of pharmaceuticals including anti-tumor agents. Neurospora crassa generates metabolites with diverse structural classes, however, its potential as an anti-tumor agent source has not been explored. The purpose of this study aimed to investigate the potential of Neurospora crassa mixture against breast cancer. The in vitro T-47D and MDA-MB-231 experiments showed that N. crassa mixture at the concentrations of both 1.7 and 0.85 µg/ml significantly inhibited tumor cell proliferation, migration and invasion, and 3D spheroid formation. However, the inhibition rates of MCF-10A ranged 10-20% at concentrations of 0.85 and 1.7 µg/ml. The mixture at the concentration of 0.85 µg/ml could significantly downregulate the expressions of transcription factors of E2F1 and E2F3, cancer stem cell-related genes of LIN28, HIWI, and CD133, and onco-lncRNA HOTAIR, and increase CASP3 activity in either T-47D or MDA-MD-231 breast cancer cell lines. In vivo breast cancer C3H mouse model results showed that N. crassa mixture significantly inhibited tumor growth. These findings suggest that N. crassa contains an antitumor component(s) against breast cancer invasiveness, which may inhibit the self-renewal and differentiation of breast cancer stem cells possibly by downregulating cancer stem cell-associated and/or transcription factor genes and oncogenes, and promoting apoptosis.
Keywords: 3D spheroid; Breast cancer; Cancer stem cells; Gene expression; Neurospora crassa.
© 2022. The Author(s), under exclusive licence to The Japanese Breast Cancer Society.