Abstract 113: Evaluating the anticancer activity of two flexible heteroarotinoid analogs on breast cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 77; no. 13_Supplement; p. 113
• Main Authors: Ginn, Emily, Zou, Hongye, Fallatah, Maryam M., Liu, Shengquan, Louie, Maggie C.
• Format: Journal Article
• Language: English
• Published: 01-07-2017
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2017-113

Abstract
Flexible heteroarotiniods (flex-hets) are compounds derived from retinoic acid and recent studies have indicated that these compounds exhibit anti-cancer activity. Amongst the flexible heteroarotinoids, SHetA2 has been to shown block the growth of cervical, head and neck, kidney, lung, and ovarian cancers, and most recently, prostate and breast cancers. However, due to SHetA2’s limitations— a high degree of hydrophobicity, non-selectivity, and potential liver toxicity— a second generation of analogs was developed. Results from our recent study suggest that one of the second-generation analogs, 1-(1-(naphthalen-1-yl)ethyl)-3-(4-nitrophenyl)thiourea (SL-1-09) exhibits anti-cancer activities against both ERα+ and ER- breast cancer cells at micromolar concentrations. Since SL-1-09 is a racemic mixture, the R (SL-1-29) and S (SL-1-30) enantiomers were purified and investigated for their anti-cancer properties. Our results suggest that SL-1-30 has greater growth inhibitory effects on T47D, MCF7, MDA-MB-453, MDA-MB-468 cells in comparison to SL1-29, suggesting that the activity observed in SL-1-09 is likely associated with the S enantiomer. Consistent with this data, breast cancer cells treated with SL-1-09 and SL-1-30 express lower levels of proteins that regulate the cell cycle (i.e, cyclin A, cyclin B, cyclin D1, cyclin E and cdk2). These results demonstrate that SL-1-30 and SL-1-09 inhibit breast cancer cell growth, potentially by blocking cell cycle progression, however further studies are necessary for determining the mechanisms of action.
Citation Format: Emily Ginn, Hongye Zou, Maryam M. Fallatah, Shengquan Liu, Maggie C. Louie. Evaluating the anticancer activity of two flexible heteroarotinoid analogs on breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 113. doi:10.1158/1538-7445.AM2017-113