Bromoenol Lactone Attenuates Nicotine-induced Breast Cancer Cell Proliferation and Migration

Author

Bethany Breakall, Eastern Kentucky UniversityFollow
Nova Arnold, Eastern Kentucky UniversityFollow
Joseph Rollins, Eastern Kentucky UniversityFollow
Lindsay E. Calderon, Eastern Kentucky UniversityFollow
Margaret Ndinguri, Eastern Kentucky UniversityFollow
Shin Liu

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Creation Date

Spring 2-13-2016

Major

Pre-medical Biology

Department

Biological Sciences

Degree

Undergraduate

Mentor

Lindsay E. Calderon

Mentor Department

Biological Sciences

Abstract

The effects of iPLA₂β (Ca²⁺-independent Phospholipase A₂β) and MMP-9 (Matrix Metalloproteinase-9) on the migration of cancer cells have been a recent focus for biomedical research and have been found to be over-expressed. However, their roles are not entirely known, especially concerning nicotine-induced breast cancer cell advancement, which has not been thoroughly investigated. The purpose of this study is to determine the involvement of iPLA₂β in nicotine-induced breast cancer cell advancement. BEL (bromoenol lactone), a suicide inhibitor of iPLA₂β, was hypothesized to decrease the intensity of the effects of nicotine-induced breast cancer. Following the BEL treatment, the in-vitro results exhibited a significant debilitation of 4T1 cell proliferation for both basal and nicotine-induced, as shown in the MTT proliferation assay. Scratch and transwell assays revealed migration was also negatively affected. The expression of MMP-9 was discovered to have behaved in an iPLA₂β-dependent manner, which further supports the idea that iPLA₂β plays a significant role, concerning the mediation of basal and nicotine-induced cancer cell progression. In-vivo results also supported this conclusion. In mice, basal and nicotine-induced tumor growth was significantly decreased, in comparison with the control group. BEL also reduced nicotine-induced HIF-1alpha, CD31, and MMP-9 tumor expression, as shown by the immunohistochemical analysis; the presence of nicotine-induced tumors in lung tissue was reduced significantly. In-vitro and in-vivo results suggest that MMP-9 behaves in an iPLA₂β-dependent manner and consequently mediates nicotine-induced breast cancer cell migration and proliferation. Because BEL was found to reduce the effects of this, it may be a possible chemotherapeutic drug.