Anticancer Impact of Nitric Oxide (NO) and NO Combination with SMYD-3 Inhibitor on Breast Carcinomas.

Jenna L Gordon,Melissa M Reynolds,Mark A Brown,Kristin J Hinsen

doi:10.3390/diseases9040082

Jenna L Gordon, Melissa M Reynolds + Show 2 more

Open Access

https://doi.org/10.3390/diseases9040082

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Abstract

Despite enormous advances in the detection and treatment of breast cancer, it still remains the leading cancer diagnosis and has the second highest mortality rate. Thus, breast cancer research is a high priority for academics and clinicians alike. Based on previous research indicating the potential of nitric oxide (NO) and SMYD-3 inhibition, this work sought to expand upon these concepts and combine the two approaches. Both NO (from S-Nitrosoglutathione (GSNO)), termed Group 1, and a combination therapeutic, inhibitor-4 (SMYD-3 inhibitor) plus NO (from GSNO), termed Group 2, were evaluated for their efficacy on breast carcinoma cell lines MCF7 and MDA-MB-231, and the normal MCF10A breast cell line, using cellular viability, colony formation capacity, cytotoxicity, and cellular apoptosis analysis. These results indicated that, in Group 1, breast carcinoma lines MCF7 and MDA-MB-231, cells experienced a moderate reduction in cellular viability (~20–25%), a large reduction in colony formation capacity (~80–90%), a moderate increase in the relative number of dead cells, and a moderate increase in cellular apoptosis. Group 2 was significantly more impactful, with a ~50% knockdown in cellular viability, a 100% reduction in colony formation capacity, a large increase in the relative number of dead cells, and a large increase in cellular apoptosis. Additionally, Group 2 induced a very small impact on the normal MCF10A cell line. Cumulatively, this work revealed the exciting impact of this combination therapeutic, indicating its potential for clinical application and further research.

Highlights

Female breast cancer cases in the United States have been continually increasing over the past 20 years [1]
The overall goal of this study was to determine the relative efficacy of nitric oxide (NO), delivered by GSNO only (Group 1), and the combination therapeutic, SMYD-3 inhibitor and NO from GSNO (Group 2) on human breast carcinomas MCF7 and MDA-MB-231
Cell Viability Assays Initially, the effects of two treatment groups, Group 1 ApoptosisGorofuNpO1 (Group 1) and Group 2, were assessed for their impact on viability of MCF7 and MDA-MB-231 cells compared to normal breast cells, MCF10A

Summary

Introduction

Female breast cancer cases in the United States have been continually increasing over the past 20 years [1]. 5-year survival rates remain optimistic [2]. This is possible because of continued advancements in breast cancer detection and treatment options. The course of treatment is dependent upon three subcategories of breast cancer that are defined by the presence or absence of specific molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2) [3,4]. Chemotherapy, endocrine therapy, and ERBB2-targeted antibody or small molecule inhibitor therapy combined with chemotherapy are mainstays in breast cancer treatment [2,5,6,7,8,9]. Breast cancer far exceeds all other cancers in new cancer diagnoses and has the second highest mortality rate [1]

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