Abstract 3268: Histological and biological effects of substituted quinolines (gap junction enhancers) in a spontaneous mammary tumor model

Abstract

Abstract Effective use of antineoplastic drugs depends on the ability to balance the killing of tumor cells against the inherent toxicity to the host. Antineoplastic agents that act primarily on rapidly dividing and growing cells produce multiple side effects and are dose limiting. In recent years, there has been the development of biologic response modifiers aimed at enhancing innate anti-tumor defense mechanisms. Previous publications showed that substituted quinolines possess potent inhibitory activities against breast cancer cells through the enhancement of gap junction intercellular communication. These drugs decrease 71% of xenograft breast tumors in nude mice. The objective of this project is to evaluate the effect of substituted quinolines in a spontaneous mouse mammary tumor model (PyVT). PyVT mice were used at three different stages (pre, early and late) to characterize histological and biological changes in the treated animals compared to controls. Substituted quinolines cause a decrease of tumor growth rate by 112%, 77%, and 57% in the pre, early, and late stages of tumor development, respectively. Treatment during the pre and early stages of tumor formation also resulted in a decrease in the total number of tumors. Western blot analysis of the pre stage tumors show that the gap junction protein connexin 43 is more expressed in treated animals compared to control and the contrary for connexin 46. In the early and late stages, connexin 43 is expressed less in treated mice than controls, and vice versa for connexin 46. The expression of these connexins in control tissue suggests that this is due to an overall increase in connexin 43 and a decrease in connexin 46 during tumor development and metastasis. Histology of vital organs showed no significant alteration in treated animals compared to controls. These findings provide evidence that substituted quinolines cause a significant tumor reduction in a spontaneous mammary tumor model with no obvious adverse effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3268. doi:1538-7445.AM2012-3268