title: Inhibition of oxidative stress-induced invasiveness of cancer cells by Ganoderma lucidum is mediated through the suppression of interleukin-8 secretion.
abstract: Epidemiological studies suggest that the intake of natural/nutrient products is inversely related to cancer risk. While oxidative stress, generating reactive oxygen species, has been linked to cancer initiation and progression, dietary antioxidants have reduced the risk of certain cancers. Experimental studies have demonstrated that antioxidants and phytochemicals could prevent cancer metastasis, and antioxidants were suggested as adjuvants in cancer therapy. Ganoderma lucidum is an Asian medicinal mushroom that has been used for the past two thousand years for the treatment of various diseases, including cancer. G. lucidum is currently popular as a dietary supplement in the form of tea, powder or extract. We have previously demonstrated that G. lucidum suppresses growth, angiogenesis and invasiveness of highly invasive and metastatic breast cancer cells. The present study was undertaken to evaluate the effect of G. lucidum on oxidative stress-induced metastatic behavior of poorly-invasive MCF-7 breast cancer cells. We show that G. lucidum inhibits oxidative stress-induced migration of MCF-7 cells by the down-regulation of MAPK signaling. G. lucidum suppressed oxidative stress stimulated phosphorylation of extracellular signal-regulated protein kinases (Erk1/2), which resulted in the down-regulation of expression of c-fos, and in the inhibition of transcription factors AP-1 and NF-kappaB. The biological effect of G. lucidum on cell migration was mediated by the suppression of secretion of interleukin-8 from MCF-7 cells exposed to oxidative stress. In summary, our results suggest that G. lucidum inhibits the oxidative stress-induced invasive behavior of breast cancer cells by modulating Erk1/2 signaling and can be potentially considered as an antioxidant in adjuvant cancer therapy.
authors.affiliation: Cancer Research Laboratory, Methodist Research Institute, Indianapolis, IN 46202, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Thyagarajan
authors.forename: Jiahua
authors.initials: J
authors.lastname: Jiang
authors.forename: Amber
authors.initials: A
authors.lastname: Hopf
authors.forename: Jiri
authors.initials: J
authors.lastname: Adamec
authors.forename: Daniel
authors.initials: D
authors.lastname: Sliva
mesh_terms: D000975:Antioxidants / Q000302:isolation & purification / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002853:Chromatography, Liquid / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects; D006538:Heptanoic Acids / Q000032:analysis / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000378:metabolism*; D007810:Lanosterol / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011134:Polysaccharides / Q000032:analysis / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020940:Reishi / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D000975:Antioxidants; D006538:Heptanoic Acids; D016209:Interleukin-8; D016328:NF-kappa B; D011134:Polysaccharides; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; C515007:ganoderic acid H; D007810:Lanosterol; C515005:ganoderic acid A; C047406:ganoderan A; D006861:Hydrogen Peroxide; C515006:ganoderic acid F; D008156:Luciferases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3