Premium
Arotinoid mofarotene (RO40‐8757) up‐regulates p21 and p27 during growth inhibition of pancreatic cancer cell lines
Author(s) -
Kawa Shigeyuki,
Nikaido Toshio,
Aoki Yuji,
Zhai Yali,
Kumagaya Toshiko,
Furihata Kenichi,
Fujii Shingo,
Kiyosawa Kendo
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19970904)72:5<906::aid-ijc31>3.0.co;2-3
Subject(s) - pancreatic cancer , growth inhibition , cancer research , cell growth , cell culture , biology , cancer , medicine , genetics
Effective chemotherapy for pancreatic cancer is urgently needed. The anti‐proliferative activity of a new retinoid, mofarotene (RO40‐8757), was compared with that of other retinoids, such as all trans ‐retinoic acid, 13‐ cis retinoic acid and 9‐ cis retinoic acid, on 9 pancreatic cancer cell lines in relation to the effects on various cell cycle–regulating factors. After treatment with each retinoid, anti‐proliferative effect was determined by the MTT method and expression of cell cycle–regulating factors, such as cyclins (D 1 , E and A), cyclin‐dependent kinases (2 and 4), cyclin‐dependent kinase inhibitors (p21 and p27) and retinoblastoma protein, was analyzed by Western blotting. Mofarotene showed half‐maximal inhibition of cell proliferation at concentrations between 0.14 × 10 −6 and 3.8 × 10 −6 mol/l with little cytotoxicity. In contrast, the other retinoids did not inhibit the growth of all cell lines by over 50% compared to controls. A marked increase in the fraction of cells in G 1 phase of the cell cycle was observed after mofarotene treatment; this was associated with marked up‐regulation of p21/p27 and a shift of retinoblastoma protein into the hypophosphorylated form. In conclusion, mofarotene inhibits the growth of pancreatic cancer cells by inducing G 1 ‐phase cell cycle–inhibitory factors (p21, p27 and hypophosphorylated form of Rb protein) and is considered to be a useful agent for pancreatic cancer treatment. Int. J. Cancer 72:906–911, 1997. © 1997 Wiley‐Liss, Inc.