Potential Block of Direct and Secondhand Smoke‐Induced Increase in Endothelin‐1 Signaling of Breast Cancer Cell Lines by Hinute‐AM

Abstract

Several epidemiological studies suggest that cigarette smoking as well as exposure to second‐hand smoke increase the incidence of breast cancer. Diet also plays an important role in breast cancer as well as other diseases. However, few studies have examined the molecular mechanisms by which cigarette smoke and diet alter breast cancer incidence. The neuropeptide hormone endothelin‐1 (ET‐1) has been identified as a multifunctional molecule that promotes cancer growth. High levels of ET‐1 expression are also associated with reduced survival of breast cancer patients. The goal of the present study was to assess whether direct or passive exposure to cigarette smoke alters the expression of ET‐1 and one of its receptors, ETAR, in non‐tumorigenic breast cells and breast cancer cell lines. To determine whether dietary factors alter this increase in ET‐1 and ETAR, cells were also exposed to Hinute‐AM, a commercially marketed soy protein hydrolysate. Proliferation assays were used to measure the effect of cigarette smoke on non‐tumorigenic breast cells. Both direct and second hand smoke exposure increased proliferation of MCF‐10, MCF‐12A and MCF‐12F non‐tumorigenic breast cell lines. We next performed Western blot analysis to test the effect of cigarette smoke of ET‐1 and ETAR expression. Exposure to direct and second‐hand cigarette smoke increased ET‐1 and ETAR protein within non‐tumorigenic MCF‐10A cells as well as BT549 and MCF‐7 breast cancer cells. Low concentrations (0.02–0.20 mg/mL) of Hinute – AM reduced proliferation of breast cancer cells and protein expression of ET‐1. In conclusion, our data suggest that cigarette smoke may increase the proliferation and aggressiveness of breast cancer by increasing expression of ET‐1 and its receptors. Furthermore, it may be possible to counteract the effects of cigarette smoke with dietary supplements such as Hinute‐AM.Support or Funding Information[Supported by Grants from Army (DAMD 17‐03‐1‐0352), FAMRI (Clinical Innovator Award 062415), Fuji Oil Company, Osaka, Japan, NCI (R25CA214220) and NIH (MeTRC5U5AMD007593).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.