Abstract
ObjectivesCalcium independent group VIA phospholipase A2 (iPLA2β) and Matrix Metalloproteinase-9 (MMP-9) are upregulated in many disease states; their involvement with cancer cell migration has been a recent subject for study. Further, the molecular mechanisms mediating nicotine-induced breast cancer cell progression have not been fully investigated. This study aims to investigate whether iPLA2β mediates nicotine-induced breast cancer cell proliferation and migration through both in-vitro and in-vivo techniques. Subsequently, the ability of Bromoenol Lactone (BEL) to attenuate the severity of nicotine-induced breast cancer was examined.Method and ResultsWe found that BEL significantly attenuated both basal and nicotine-induced 4T1 breast cancer cell proliferation, via an MTT proliferation assay. Breast cancer cell migration was examined by both a scratch and transwell assay, in which, BEL was found to significantly decrease both basal and nicotine-induced migration. Additionally, nicotine-induced MMP-9 expression was found to be mediated in an iPLA2β dependent manner. These results suggest that iPLA2β plays a critical role in mediating both basal and nicotine-induced breast cancer cell proliferation and migration in-vitro. In an in-vivo mouse breast cancer model, BEL treatment was found to significantly reduce both basal (p<0.05) and nicotine-induced tumor growth (p<0.01). Immunohistochemical analysis showed BEL decreased nicotine-induced MMP-9, HIF-1alpha, and CD31 tumor tissue expression. Subsequently, BEL was observed to reduce nicotine-induced lung metastasis.ConclusionThe present study indicates that nicotine-induced migration is mediated by MMP-9 production in an iPLA2β dependent manner. Our data suggests that BEL is a possible chemotherapeutic agent as it was found to reduce both nicotine-induced breast cancer tumor growth and lung metastasis.
Highlights
According to the American Cancer Society, Cancer Facts & Figures 2015, there are an estimated 1,658,370 new cancer cases diagnosed in the United States, of which 231,840 are attributed to breast cancer with 40,290 deaths
We found that Bromoenol Lactone (BEL) significantly attenuated both basal and nicotine-induced 4T1 breast cancer cell proliferation, via an MTT proliferation assay
These results suggest that iPLA2β plays a critical role in mediating both basal and nicotine-induced breast cancer cell proliferation and migration in-vitro
Summary
According to the American Cancer Society, Cancer Facts & Figures 2015, there are an estimated 1,658,370 new cancer cases diagnosed in the United States, of which 231,840 are attributed to breast cancer with 40,290 deaths. 10–15% of breast cancer patients develop distant metastases within 3 years after the identification of a primary tumor, and remain at risk for metastatic disease during their entire lifespan [4]. Smoke exposure has been found to increase anchorage-independent growth, motility, and invasiveness of breast cancer cells leading to higher rates of cell survival, colonization [8] and metastasis. Cigarette smoke was found to significantly increase breast cancer mortality by 60% and the probability of recurrence by 41% [15]. Nicotine is a known toxicant found in smoke that is linked to breast cancer apoptosis resistance, tumor growth, and migration, along with, facilitating angiogenic metastasis [9,17,18,19,20]. The exact cellular mechanisms promoting nicotine-induced breast cancer cell proliferation and migration remain undetermined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
