In this study, electrical impedance-based measurements were used to distinguish oral cancer cells and non-cancer oral epithelial cells based on their cellular activities on the microelectrodes in a real-time and label-free manner. CAL 27 and Het-1A cell lines were used as the models of oral cancer cells and non-cancer oral epithelial cells, respectively. Various cellular activities, including cell adhesion, spreading, and proliferation were monitored. We found that both the kinetics of cell spreading and the static impedance-based cell index were feasible to distinguish the two cell types. At each given cell number, CAL 27 cell spreading produced a smaller cell index change rate that was 60-70% of those of Het-1A cells. When cells were fully spread, CAL 27 cells generated a cell index more than four times greater than that of Het-1A cells. Since cell spreading and attachment occurs in the first few hours when they were cultured on the microelectrodes, this impedance-based method could be a rapid label-free and non-invasive approach to distinguish oral cancer cells from non-cancer oral epithelial cells. Cell viability analysis was performed along with the impedance-based analysis. Confocal microscopic imaging analysis showed the difference in cell morphology and the thickness of cell monolayers between the two cell types.

Prostate cancer constitutes a serious health challenge and remains one of the main causes of cancer-related death among men. The more aggressive form of the disease has been attributed to androgen independence; resulting in lack of response to androgen deprivation therapy and sustained activation of other growth pathways. The scaffold proteins β-arrestin 1 and 2 (βarr1 and βarr2) which are known to mediate G protein-coupled receptor desensitization and internalization, were also shown to modulate prostate tumorigenesis. βarr1 is significantly overexpressed (>4 fold) in prostate cancer cells relative to βarr2. In this study, we investigated the effect of βarr1 overexpression in prostate cancer development and progression using the mouse and human PCa cell xenografts, and autochthonous transgenic adenocarcinoma mouse prostate (TRAMP) models deficient in β-arrestins Depletion of βarr1 in TRAMP mice (TRAMP/βarr1 -/-) increased PCa growth and decreased overall survival relative to control TRAMP or TRAMP/βarr2 -/- animals. Prostate tissues from TRAMP/βarr1 -/- tumors displayed an increase in androgen receptor expression whereas overexpression of βarr1 in TRAMP-C1 (TRAMP-C1-βarr1-GFP) which derived from TRAMP decreased AR expression, cell proliferation and tumor growth in nude mice xenografts, relative to control TRAMP-C1-GFP. Knockdown of βarr1 expression in human MDA PCa 2b cells (MDA PCa 2b-βarr1 -/-) also decreased AR expression cell proliferation and tumor growth relative to control (MDA PCa 2b-Sham) cells. Interestingly, both TRAMP-C1-βarr1-GFP and MDA PCa 2b-βarr1 -/- xenografts showed a decrease in AKT phosphorylation, but an increase MAPK activation. Altogether, the data indicate that the effect of βarr1 in modulating AR signaling to regulate prostate cancer aggressiveness is cell and host autonomous.

Ginger active components are widely known for being a potent antioxidant and recently as a potential anticancer agent. [6]-Gingerol, the most abundant and pungent bioactive component of ginger, was shown to inhibit angiogenesis and tumorigenesis in xenograph models of both prostate cancer (PCa) and melanoma. To date, the precise mechanism(s) for the antitumor effect of ginger is not well understood. The adaptor proteins, β-arrestins, have been shown to modulate tumor development and metastasis in both PCa and melanoma. In this study, we sought to determine the role of [6]-gingerol in β-arrestin (βarr) 1 and 2-mediated PCa and melanoma development, progression, and metastasis. To that end, the PCa cells PC-3 and the melanoma B16-F10 cells were treated with different concentrations of [6]-gingerol for 48 hours. Cell lysates were assayed by Western blot analysis for βarr-1 and βarr-2, CXCR1, and CXCR2 expression, as well as MAP kinase and transcription factors activation. The data demonstrated that pretreatment with [6]-gingerol caused a dose-dependent inhibition of βarr-2, but not βarr-1, in both cell lines, which correlated with significant decrease in Akt and NF-κB activation. [6]-Gingerol pretreatment decreased CXCR1 and CXCR2 expression, CXCL-8-induced intracellular calcium mobilization; and delayed wound closure. [6]-Gingerol exposure also decreased PC-3 and B16 metastasis in zebrafish. Altogether the data indicated that the protective effect of [6]-gingerol in tumorigenesis is likely mediated via a βarr-2-dependent mechanism. Citation Format: Tonelia A. Mowart, Timothy Adekoya, Nikia Smith, Tonya S. Lane, Ricardo M. Richardson. Ginger consumption inhibits β-arrestin-2 expression and functions in melanoma and prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr B005.

Ginger active components are widely known for being a potent antioxidant and recently as a potential anticancer agent. To date, the precise mechanism(s) for the antitumor effect of ginger is not well understood. An active chemical component of ginger, 6-gingerol, was recently shown to inhibit angiogenesis and tumorigenesis. In this study we investigated the role of ginger in prostate cancer growth and proliferation using PCa cell lines from African American (AA) and Caucasian American (CA) men. To that end, MDA-PCa 2b (AA), LnCap (CA) and PC-3 (CA) cells were treated with different concentrations of 6-gingerol or 6-shogaol for 24 hours and cell proliferations were measured by XTT assay. To determine the effect of 6-gingerol in cell signaling, cell lysates were assayed for β-arrestin 1 and 2 expression, MAP kinase and caspase activity by Western Blotting. The data demonstrated that 6-gingerol inhibits cellular proliferation and promotes apoptosis in both AA and CA PCa cell lines. These effects correlated with decrease in β -arrestin 2, not β -arrestin 1, expression and Akt phosphorylation but increased caspase activity. Taken together the data suggests that 6-gingerol inhibits PCa growth and promotes PCa apoptosis via a βarr-2/Akt-dependent mechanism. Since PC-3 cells do not express AR, the data likely indicates that 6-gingerol effect is independent of AR activation and PSA expression. Citation Format: Tonya S. Lane, Ricardo M. Richardson. Ginger consumption may delay the onset of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1960. doi:10.1158/1538-7445.AM2015-1960