Antrodia salmonea suppresses epithelial-mesenchymal transition/metastasis and Warburg effects by inhibiting Twist and HIF-1α expression in Twist-overexpressing head and neck squamous cell carcinoma cells.

Jhih-Hsuan Hseu, Yi-An Lin, Sudhir Pandey, Chithravel Vadivalagan, Asif Ali, Siang-Jyun Chen, Tzong-Der Way, Hsin-Ling Yang, You-Cheng Hseu

Journal: Journal of ethnopharmacology 2023;318(Pt B):117030

PMID: 37572931

Full Text on Elsevier Science View on PubMed

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Antrodia salmonea (AS), linked to the genus Taiwanofungus, is a medicinal fungus, and exhibits anti-inflammatory, anti-oxidant, and tumor inhibiting properties.

AIM OF THE STUDY

In this study, we investigated the metabolic reprogramming and anti-metastasis/epithelial-mesenchymal transition (EMT) effects of AS exposure in Twist-overexpressing head and neck squamous cell carcinoma (HNSCC, OECM-1 and FaDu-Twist) cells.

MATERIALS AND METHODS

MTT assay, Western blot, migration/invasion assay, immunofluorescence, glucose uptake assay, lactate assay, oxygen consumption rate (OCR)/Extracellular acidification rate (ECAR) assay, Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS), and qRT-PCR experimental techniques were used to evaluate the therapeutic potential of AS treatment in HNSCC cells.

RESULTS

This study showed that AS exhibits anti-EMT and anti-metastatic effects as well as metabolic reprogramming in Twist-overexpressing HNSCC cells. AS exposure inhibited Twist and hypoxia-inducible factor-1α (HIF-1α) protein and/or mRNA expression in Twist-overexpressing OECM-1 and FaDu-Twist cells. AS markedly suppressed EMT by enhancing the expression of E-cadherin; while the N-cadherin was suppressed. Furthermore, glucose uptake and lactate accumulation, together with HIF-1α-regulated glycolysis genes were diminished by AS in OECM-1 cells. AS decreased the ECAR, and enhanced the OCR together with basal respiration, ATP production, maximal respiration, and spare respiratory capacity under normoxia and hypoxia (CoCl) in OECM-1 cells. There was a marked reduction in the level of glycolytic intermediate's; while TCA cycle metabolites were increased by AS treatment in OECM-1 cells.

CONCLUSIONS

We concluded that AS treatment suppresses EMT/metastasis and Warburg effects through Twist and HIF-1α inhibition in Twist-overexpressing HNSCC cells.

Address: Department of Dermatology, China Medical University Hospital, Taichung, 404327, Taiwan.; Institute of Nutrition, College of Health Care, China Medical University, Taichung, 406040, Taiwan.; Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, 406040, Taiwan.; Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI, 48109, United States.; Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Sanat Nagar, Srinagar, Jammu and Kashmir, 190005, India.; Department of Life Sciences, China Medical University, Taichung, 406040, Taiwan.; Institute of Nutrition, College of Health Care, China Medical University, Taichung, 406040, Taiwan. Electronic address: [email protected].; Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, 406040, Taiwan; Department of Health and Nutrition Biotechnology, Asia University, Taichung, 413305, Taiwan; Chinese Medicine Research Center, China Medical University, Taichung, 404333, Taiwan; Research Center of Chinese Herbal Medicine, China Medical University, Taichung, 404333, Taiwan. Electronic address: [email protected].

DOI: 10.1016/j.jep.2023.117030

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MeSH Terms: Head and Neck Neoplasms, Epithelial-Mesenchymal Transition, Polyporales, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Line, Tumor, Gene Expression Regulation, Neoplastic, Glucose, Humans, Squamous Cell Carcinoma of Head and Neck