title: p38MAPK and Rho-dependent kinase are involved in anoikis induced by anicequol or 25-hydroxycholesterol in DLD-1 colon cancer cells.
abstract: Anchorage-independent growth is evidence of the malignant transformation of cells. We previously reported the characterization of anicequol, a novel inhibitor of the anchorage-independent growth of tumor cells, and here we show that the effects of 25-hydroxycholesterol (25-HC) on colon cancer cells were very similar to those of anicequol. By analyzing the effects of inhibitors and performing RNA interference experiments, we found that p38 mitogen-activated protein kinase (p38MAPK) was involved in anicequol- and 25-HC-induced anoikis in DLD-1 cells. In addition, Rho-associated, coiled-coil containing protein kinase (ROCK) was also associated with anoikis induced by anicequol or 25-HC. Taken together, our findings suggest that activation of the p38MAPK and ROCK pathways might provide a new therapeutic strategy against cancer, and raise the possibility that tumor metastasis is influenced by 25-HC under physiological conditions.
authors.affiliation: Department of Microbial Chemical Biology and Drug Discovery, Iwate Medical University School of Pharmacy, 2-1-1 Nishitokuta, Yahaba, Shiwa-gun, Iwate 020-3694, Japan.
authors.forename: Arowu R
authors.initials: AR
authors.lastname: Tanaka
authors.forename: Kohji
authors.initials: K
authors.lastname: Noguchi
authors.forename: Hidesuke
authors.initials: H
authors.lastname: Fukazawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Igarashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Uehara
mesh_terms: D023102:Anoikis / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000201:enzymology*; D004875:Ergosterol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D034622:RNA Interference; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D006888:Hydroxycholesterols; C458888:anicequol; C007997:25-hydroxycholesterol; D054460:rho-Associated Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004875:Ergosterol