title: Suppression of cancer stem-like phenotypes in NCI-H460 lung cancer cells by vanillin through an Akt-dependent pathway.
abstract: Cancer stem cells (CSCs) have been reported as a major cause of cancer metastasis and the failure of cancer treatment. Cumulative studies have indicated that protein kinase B (Akt) and its downstream signaling pathway, including CSC markers, play a critical role in the aggressive behavior of this cancer. In this study, we investigated whether vanillin, a major component in Vanilla planifolia seed, could suppress cancer stemness phenotypes and related proteins in the human non-small cell lung cancer NCI‑H460 cell line. A non-toxic concentration of vanillin suppressed spheroid and colony formation, two hallmarks of the cancer stemness phenotype, in vitro in NCI‑H460 cells. Western blot analysis revealed that the CSC markers CD133 and ALDH1A1 and the associated transcription factors, Oct4 and Nanog, were extensively downregulated by vanillin. Vanillin also attenuated the expression and activity of Akt, a transcription regulator upstream of CSCs, an action that was confirmed by treatment with the Akt inhibitor perifosine. Furthermore, the ubiquitination of Akt was elevated in response to vanillin treatment prior to proteasomal degradation. This finding indicates that vanillin can inhibit cancer stem cell-like behavior in NCI‑H460 cells through the induction of Akt-proteasomal degradation and reduction of downstream CSC transcription factors. This inhibitory effect of vanillin may be an alternative approach in the treatment against lung cancer metastasis and its resistance to chemotherapy.
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Songpol
authors.initials: S
authors.lastname: Srinual
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
authors.affiliation: Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Varisa
authors.initials: V
authors.lastname: Pongrakhananon
mesh_terms: D000071916:AC133 Antigen / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D001547:Benzaldehydes / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D045744:Cell Line, Tumor; D003114:Colony-Forming Units Assay; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000071317:Nanog Homeobox Protein / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050697:Retinal Dehydrogenase; D015398:Signal Transduction / Q000187:drug effects*; D018874:Spheroids, Cellular / Q000187:drug effects; D031669:Vanilla / Q000737:chemistry
chemical_list: D000071916:AC133 Antigen; D001547:Benzaldehydes; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D010767:Phosphorylcholine; C105905:perifosine; C100058:vanillin; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex