Prostate cancer is a major health problem and a significant cause of mortality in men woridwide. Family history and race are the two major risk factors for this disease. The age-adjusted incidence rate and mortality rate of prostate cancer is significantly higher in African-Americans compared to Caucasian-Americans or other races in the US and woridwide. Thus, an understanding of the molecular mechanism responsible for the development and progression of prostate cancer is extremely important to the development of more effective therapeutic strategies. Cannabinoids (including endocannabinoids) regulate cell death or cell growth, depending on the cell type and concentration of the cannabinoid. Cannabinoids inhibit the growrth of prostate cancer cells. We have found that activation of cannabinoid receptor-2 (CB2) inhibits androgen-sensitive prostate cancer (AS PC) cell proliferation and motility. Our preliminary data also suggest that cannabinoid compounds possess selective efficacy, producing less adverse effects on nornial prostate epithelial cells compared to LNCaP prostate cancer cells. To date most of the anti-tumor effects of cannabinoids have been correlated with the CBI receptors rather than CB2 receptor activation, although CB2 receptor expression is high in many tumor tissues including prostate tumor. However downstream mechanisms mediating anti-tumor effects of cannabinoids under in vivo conditions are poorly understood. Further, CB1 receptors are highly expressed in neuronal cells and brain tissue. Therefore, unlike activation of CB2 receptors, CB1 receptor activation produces neurobehavioral and psychotropic side effects. Thus, CB2 receptor-mediated therapeutic intervention of prostate cancer has clinical advantages. Based on our preliminary data we hypothesize that activation of CB2 receptor inhibits androgen-sensitive prostate cancer (AS PC) growrth. To test this hypothesis, we have developed the following 2 specific aims: (1) To determine the effects of CB2 receptor activation on cultured LNCaP and LAPC4 prostate cancer cell proliferation, viability and migration in relation to activation of RhoA and the focal adhesion kinase (FAK) signaling pathway;and (2) To detemiine the effects of exogenous activation of CB2 receptor and increase in endogenous cannabinoid activity on AS prostate cancer growth in mice in relation to FAK activity.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA156735-03
Application #
8381982
Study Section
Special Emphasis Panel (ZCA1-SRLB-3)
Project Start
Project End
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$184,447
Indirect Cost
Name
North Carolina Central University
Department
Type
DUNS #
783691801
City
Durham
State
NC
Country
United States
Zip Code
27707
Liu, Yongjing; Xiong, Zhaohui; Beasley, Andrea et al. (2016) Personalized and targeted therapy of esophageal squamous cell carcinoma: an update. Ann N Y Acad Sci 1381:66-73
Zhao, Qingxia; Zhao, Ming; Parris, Amanda B et al. (2016) Genistein targets the cancerous inhibitor of PP2A to induce growth inhibition and apoptosis in breast cancer cells. Int J Oncol 49:1203-10
Li, Jing; Chen, Xiaoxin Luke; Shaker, Anisa et al. (2016) Contribution of immunomodulators to gastroesophageal reflux disease and its complications: stromal cells, interleukin 4, and adiponectin. Ann N Y Acad Sci 1380:183-194
Ahmad, Syed; Johnson, Gary L; Scott, John E (2015) Identification of ponatinib and other known kinase inhibitors with potent MEKK2 inhibitory activity. Biochem Biophys Res Commun 463:888-93
Chen, Hao; Beasley, Andrea; Hu, Yuhui et al. (2015) A Zebrafish Model for Studies on Esophageal Epithelial Biology. PLoS One 10:e0143878
Reaves, Denise K; Ginsburg, Erika; Bang, John J et al. (2015) Persistent organic pollutants and obesity: are they potential mechanisms for breast cancer promotion? Endocr Relat Cancer 22:R69-86
D'Arcy, Monica; Fleming, Jodie; Robinson, Whitney R et al. (2015) Race-associated biological differences among Luminal A breast tumors. Breast Cancer Res Treat 152:437-48
Li, Puyu; Zhao, Ming; Parris, Amanda B et al. (2015) p53 is required for metformin-induced growth inhibition, senescence and apoptosis in breast cancer cells. Biochem Biophys Res Commun 464:1267-74
Hood, Sula; Linnan, Laura; Jolly, David et al. (2015) Using the PRECEDE Planning Approach to Develop a Physical Activity Intervention for African American Men Who Visit Barbershops: Results From the FITShop Study. Am J Mens Health 9:262-73
House, Alan J; Daye, Laura R; Tarpley, Michael et al. (2015) Design and characterization of a photo-activatable hedgehog probe that mimics the natural lipidated form. Arch Biochem Biophys 567:66-74

Showing the most recent 10 out of 41 publications