The RARγ selective agonist CD437 inhibits gastric cell growth through the mechanism of apoptosis

Retinoids are differentiation-inducing agents that exhibit multiple functions. Their activities are mediated through interaction with nuclear retinoic acid receptors (RAR) and retinoid X receptors (RXR). We have investigated the activities of synthetic retinoids on the growth of five gastric cancer cell lines. The effects of agonists selective for RARα, RARβ and RARγ (AM580, CD2019 and CD437, respectively) on cell growth were determined, in comparison to all-trans retinoic acid, by measuring total cellular DNA. AM580 and CD2019 had little or no effect on the growth of all five cell lines. In contrast, the RARγ agonist CD437 inhibited cell growth up to 90–99% in both retinoic acid sensitive and resistant gastric cancer cells at a concentration of 1 μM. The growth suppression caused by CD437 was accompanied by the induction of apoptosis as judged by morphological criteria and DNA ladder formation. However, the extent of CD437-induced growth suppression was not correlated with RARγ mRNA levels, which indicates that CD437 induces apoptosis in gastric cancer cells via an RARγ independent pathway.