4.7 Article

Bifunctional mechanisms of autophagy and apoptosis regulations in melanoma from Bacillus subtilis natto fermentation extract

Journal

FOOD AND CHEMICAL TOXICOLOGY
Volume 150, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2021.112020

Keywords

Bacillus subtilis natto Extract; Melanoma; Oxidative stress; Autophagy; Apoptosis

Funding

  1. Ministry of Science and Technology, Taiwan [MOST 108-2221-E 005-044, MOST 1092221-E 005-012]
  2. National Chung Hsing University, Taiwan [ENABLE 110ST001G, ENABLE 108ST001B]

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NFDE and NWE, isolated from fermented soybeans, showed significant anti-melanoma effects in cell cytotoxicity assays. The extracts increased oxidative stress in melanoma cells, shifting cellular death from autophagy to apoptosis.
Melanoma is one of the most dangerous malignant epidermal cancers. Natto freeze-drying extract (NFDE) and natto water extract (NWE) were isolated from natto, soybeans fermented by Bacillus subtilis natto, which were assessed as potential anti-melanoma agents. Cell cytotoxicity assays revealed significant anti-melanoma effects of NFDE and NWE in a dose-dependent manner, and exhibited low influences on normal skin cells, including Hs68, HaCaT and adipose tissue-derived stem cells (ADSCs), respectively. Through a flow cytometer assay and autophagy acridine orange staining, the cellular death phenomenon shifted from autophagy to apoptosis with the increased dosages. Reactive oxygen species (ROS) were enhanced using DCFDA (2,7-dichlorodihydrofluorescein diacetate) staining when melanoma cells were treated with the extract. NFDE and NWE treatments increase the oxidative stress of cancer cells and cause apoptosis by inhibiting AMP-activated protein kinase (AMPK). NFDE and NWE were considered to play a critical role in cell death through ROS adjustment, autophagy regulation and apoptosis promotion.

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