Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells

Yq, Liu; Kyle, Edward; Patel, Sajni; Housseau, Franck; Hakim, Frances T.; Lieberman, Ronald; Pins, Michael; Mv, Blagosklonny; Bergan, R. C.

doi:10.1038/sj.pcan.4500506

Cited by 25 publications

(37 citation statements)

References 35 publications

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“…The ability of PC3-M cells to rapidly cycle between cell attachment and cell detachment is consistent with their metastatic phenotype, which we and others have previously characterized (Bergan et al, 1996b;Kozlowski et al, 1984;Kyle et al, 1997;Liu et al, 2001). Importantly, PC3-M cells underwent spontaneous cell detachment in vitro, thereby providing a unique model with which to identify responsible regulatory factors.…”

Section: Discussionmentioning

confidence: 64%

“…The origins and culture conditions for PC3, metastatic variant PC3-M, human papillomavirus (HPV) transformed paired (i.e., from the same patient) normal epithelial and primary cancer 1532NPTX (normal) and 1532CPTX (cancer), and 1542NPTX (normal) and 1542CP3TX (cancer) cells (a generous gift from S Topolian, National Cancer Institute, Bethesda, MD, USA), and normal prostate epithelial cells (NPECs), have been previously described (Bright et al, 1997;Kozlowski et al, 1984;Liu et al, 2001).…”

Section: Cell Culturementioning

confidence: 99%

“…No change in endoglin expression was observed when transcript levels were compared between cells which had been adherent for 24 h (stably attached), and those which were immediately post detachment (time 0). Prior studies indicate significant changes in both structural proteins as well as cellular energy requirements during changes in cell adhesion (Bergan et al, 1996b;Liu et al, 2000Liu et al, , 2001. Thus, levels of gene expression were compared between equal numbers of cells, and equal gel loading confirmed by ethidium bromide staining of total RNA.…”

Section: Endoglin Is Down-regulated During Prostate Cell Detachmentmentioning

confidence: 99%

“…Cell adhesion assays were performed as previously described (Bergan et al, 1996b;Liu et al, 2001). Briefly, exponentially growing non-confluent cells were detached by trypsin/EDTA (Biofluids), and 10 4 cells added to each well of a 96-well culture plate (Corning Costar, Cambridge, MA, USA), in replicates of 4 -8.…”

Section: Cell Adhesion Assaymentioning

confidence: 99%

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Over expression of endoglin in human prostate cancer suppresses cell detachment, migration and invasion

et al. 2002

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The regulation of cell adhesion and motility in human prostate is not well understood. We have previously shown that the endoglin gene is differently expressed during changes in prostate cell adhesion. Endoglin is a transmembrane transforming growth factor b binding protein typically expressed by endothelial cells. In this report we demonstrate that endoglin over expression increases prostate cell attachment, while decreasing migration and invasion. Engineered decreases in endoglin expression have opposite effects. While endoglin exerted only relatively small effects upon cell adhesion, large effects upon cell migration and invasion were observed. Endoglin was shown to localize to focal adhesion plaques, consistent with its role in regulating cell adhesion and motility. Loss of endoglin expression in cancer, as compared to normal prostate, was seen in human prostate cell lines. Suppression of endoglin expression in a panel of normal human prostate cell lines led to cell detachment. Endoglin is identified as a regulator of cell adhesion, motility and invasion in human prostate. Loss of endoglin expression appears to be associated with prostate cancer progression, at least in vitro.

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Section: Discussionmentioning

confidence: 64%

Section: Cell Culturementioning

confidence: 99%

Section: Endoglin Is Down-regulated During Prostate Cell Detachmentmentioning

confidence: 99%

Section: Cell Adhesion Assaymentioning

confidence: 99%

See 2 more Smart Citations

Over expression of endoglin in human prostate cancer suppresses cell detachment, migration and invasion

et al. 2002

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“…Changes in cell adhesion and mobility contribute to the metastatic phenotype in human prostate cancer (Paul et al, 1997;Liu et al, 2000Liu et al, , 2001Liu et al, , 2002Ozen and Pathak, 2000). The manner by which prostate cells regulate these processes, however, is not well understood.…”

Section: Introductionmentioning

confidence: 99%

p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion

et al. 2003

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Transforming growth factor beta (TGFb) regulates cell adhesion, proliferation, and differentiation in a variety of cells. Smad proteins are receptor-activated transcription factors that translocate to the nucleus in response to TGFb. We demonstrate here that TGFb increases cell adhesion in metastatic PC3-M prostate cancer cells. TGFb treatment of PC3-M cells leads to nuclear translocation of R-Smad proteins. We show that Smad proteins are necessary, but not sufficient, for TGFbmediated cell adhesion. After showing that TGFb upregulated p38 MAP kinase activity in PC3-M cells, we show that inhibition of p38 MAP kinase partially blocked TGFb-mediated increase in cell adhesion, as well as nuclear translocation of Smad3. Finally, we show that Smad3 is phosphorylated by p38 MAP kinase in vitro. These findings implicate crosstalk between the MAP kinase and Smad signaling pathways in TGFb's regulation of cell adhesion in human prostate cells. This represents a mechanism by which the pleiotropic effects of TGFb may be channeled to modulate cell adhesion.

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Inhibition of HIF‐1 alpha and VEGF expression by the chemopreventive bioflavonoid apigenin is accompanied by Akt inhibition in human prostate carcinoma PC3‐M cells

Mirzoeva

Kim

Chiu

et al. 2008

Molecular Carcinogenesis

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Progression of cancer leads to hypoxic solid tumors that mount specific cell signaling responses to low oxygen conditions. An important objective of anti-cancer therapy is the development of new drugs that suppress hypoxic responses in solid tumors. Apigenin is a natural flavone that has been shown to have chemopreventive and/or anti-cancer properties against a number of tumor types. However, the mechanisms underlying apigenin's chemopreventive properties are not yet completely understood. In this study, we have investigated the effects of apigenin on expression of hypoxia-inducible factor-1 (HIF-1) in human metastatic prostate PC3-M cancer cells. We found that hypoxia induced a time-dependent increase in the level of HIF-1alpha subunit protein in PC3-M cells, and treatment with apigenin markedly decreased HIF-1alpha expression under both normoxic and hypoxic conditions. Further, apigenin prevented the activation of the HIF-1 downstream target gene vascular endothelial growth factor (VEGF). We then showed that apigenin inhibited expression of HIF-1alpha by reducing stability of the protein as well as by reducing the level of HIF-1alpha mRNA. We also found that apigenin inhibited Akt and GSK-3beta phosphorylation in PC3-M cells. Further experiments demonstrated that constitutively active Akt blunted the effect of apigenin on HIF-1alpha expression. Taken together, our results identify apigenin as a bioflavonoid that inhibits hypoxia-activated pathways linked to cancer progression in human prostate cancer, in particular the PI3K/Akt/GSK-3 pathway. Further studies on the mechanism of action of apigenin will likely provide new insight into its applicability for pharmacologic targeting of HIF-1alpha for cancer therapeutic or chemopreventive purposes.

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Prostate cancer chemoprevention agents exhibit selective activity against early stage prostate cancer cells

Cited by 25 publications

References 35 publications

Over expression of endoglin in human prostate cancer suppresses cell detachment, migration and invasion

Over expression of endoglin in human prostate cancer suppresses cell detachment, migration and invasion

p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion

Inhibition of HIF‐1 alpha and VEGF expression by the chemopreventive bioflavonoid apigenin is accompanied by Akt inhibition in human prostate carcinoma PC3‐M cells

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