Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a <i>Phellodendron Amurense</i> Bark Extract

Kumar, Addanki P.; Bhaskaran, Shylesh; Ganapathy, Manonmani; Crosby, Katherine; Davis, M. Duff; Kochunov, Peter; Schoolfield, John; Yeh, I‐Tien; Troyer, Dean A.; Ghosh, Rita

doi:10.1158/1078-0432.ccr-06-2974

Cited by 90 publications

(89 citation statements)

References 55 publications

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“…(29,30) This is one of the most important signaling pathways involved in the negative regulation of autophagy. (31) Therefore, it is possible to speculate that berberine might induce autophagy in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

Hou

Xu²,

Liu

et al. 2011

Cancer Science

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The isoquinoline plant alkaloid berberine has anti-tumor effects on a variety of carcinoma cells, mainly through inhibition of cell proliferation, apoptosis induction and cell cycle arrest. However, the mechanisms underlying its role in tumor progression are unknown. In the present study, we investigated the molecular mechanisms involved in berberine-induced cell death in human hepatoma carcinoma cell (HCC) lines HepG2 and SMMC7721. Our results showed that berberine inhibited tumor cell viability in a dose-and time-dependent manner, and induced cell death via apoptosis and autophagy. Moreover, berberine treatment significantly inhibited CD147 expression by HCC cells in a dosedependent manner. Overexpression of CD147 protein markedly reduced berberine-induced cell death. Our data provide the first experimental evidence that berberine induces cell death in HCC cells via downregulation of CD147 and suggest a new mechanism to explain its anti-tumor effects. (Cancer Sci 2011; 102: 1287-1292 B erberine is an isoquinoline alkaloid found in a number of important medicinal plant species such as Berberis aristata and Berberis aquifolium, and has antibacterial,(1) anti-hypertensive, (2) anti-inflammatory, (3) anti-diabetic (4) and anti-hyperlipidemic effects.(5) Recently, researchers have become interested in the anti-neoplastic activities of berberine and have demonstrated its anticancer effects against a variety of human cancer cells both in vitro and in vivo through suppression of tumor cell proliferation, induction of tumor cell apoptosis, and inhibition of both tumor invasion and metastasis.(6,7) These findings suggest that berberine is a promising candidate for clinical use in cancer chemotherapy.Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the third leading cause of death from cancer because of its very poor prognosis. More than 1 million cases of HCC occur in the world each year.(8) Hepatocellular carcinoma is highly resistant to conventional systemic therapies and the prognosis for patients with advanced HCC remains poor. Although a lot of progress has been made in terms of chemotherapy, which provides significant survival benefits for patients with HCC, it is associated with significant side-effects, highlighting the need for therapeutic strategies that target tumor cells without compromising normal tissue function.(9,10) Thus, the development of novel systemic agents from natural products with low toxicity and few side-effects is being actively pursued. (11)(12)(13) Previous studies confirm the anti-tumor effects of berberine on HCC. (14)(15)(16) Berberine acts by inhibiting proliferation and inducing apoptosis in HCC cells. It can also inhibit the migration of HCC cells by downregulating the Rho ⁄ ROCK signaling pathway.(17) However, the exact mechanisms underlying the anti-tumor effects of berberine are still unknown. CD147, a glycosylated immunoglobulin super family transmembrane protein, is highly expressed by HCC cells. Several in vitro studies suggest that CD147 promotes...

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Section: Discussionmentioning

confidence: 99%

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

Hou

Xu²,

Liu

et al. 2011

Cancer Science

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“…1, 2). CREB can be phosphorylated by many different protein kinases, including protein kinase A (PKA), protein kinase B (PKB)/Akt, mitogen-activated protein kinases (MAPK), and p90 ribosomal S6 kinase (p90 metastasis (4,11,12). However, a direct link between oncogenic transformation and CREB has not yet been determined.…”

Section: Introductionmentioning

confidence: 99%

HER-2/neu Mediates Oncogenic Transformation via Altered CREB Expression and Function

Steven

Leisz

Massa

et al. 2013

Molecular Cancer Research

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The cyclic (c)AMP responsive element binding protein (CREB) plays a key role in many cellular processes, including differentiation, proliferation, and signal transduction. Furthermore, CREB overexpression was found in tumors of distinct origin and evidence suggests an association with tumorigenicity. To establish a mechanistic link between HER-2/neu-mediated transformation and CREB protein expression and function, in vitro models of HER-2/neu-overexpressing and HER-2/neu-negative/silenced counterparts as well as human mammary carcinoma lesions with defined HER-2/neu status were used. HER-2/neu overexpression resulted in the induction and activation of CREB protein in vitro and in vivo, whereas short hairpin RNA (shRNA)-mediated inhibition of HER-2/neu correlated with downregulated CREB activity. CREB activation in HER-2/neu-transformed cells enhanced distinct signal transduction pathways, whereas their inhibition negatively interfered with CREB expression and/or activation. CREB downregulation in HER-2/neu-transformed cells by shRNA and by the inhibitors KG-501 and lapatinib caused morphologic changes, reduced cell proliferation with G 0 -G 1 cell-cycle arrest, which was rescued by CREB expression. This was accompanied by reduced cell migration, wound healing, an increased fibronectin adherence, invasion, and matrix metalloproteinase expression. In vivo shCREB-HER-2/neu þ cells, but not control cells, exerted a significantly decreased tumorgenicity that was associated with decreased proliferative capacity, enhanced apoptosis, and increased frequency of T lymphocytes in peripheral blood mononuclear cells. Thus, CREB plays an important role in the HER-2/neu-mediated transformation by altering in vitro and in vivo growth characteristics.

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“…For instance, Nexrutine, a herbal extract derived from Phellodendron amurense, has been investigated for its effects against prostate cancer (27,28). Our group is particularly interested in herbs used in traditional east Asian medicine, and S. delavayi Diels.…”

Section: Discussionmentioning

confidence: 99%

Stephania delavayi Diels. inhibits breast carcinoma proliferation through the p38 MAPK/NF-κB/COX-2 pathway

Park

Xu²,

Shim³

et al. 2011

Oncol Rep

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Abstract. the nuclear factor κB (NF-κB)/inhibitor of κ kinase-β (IKKβ) signaling pathway is important in tumor promotion and progression. MDA-MB-231 human breast carcinoma cells express COX-2 and show a constitutive phosphorylation of NF-κB. Many non-specific inhibitors of IKKβ and NF-κB are used to inhibit tumor promotion and progression. the Stephania delavayi Diels. (S. delavayi Diels.) extract has been reported to safely activate B cell immunity and there is evidence suggesting that it may be a promising new anticancer therapeutic agent. S. delavayi Diels. extract suppressed proliferation of the breast cancer cell lines MDA-MB-231 and MCF-7 by inducing cell death. to aid in the development of the S. delavayi Diels. extract as a therapeutic agent, its mechanisms of action were investigated, in particular its effects on p38 MApK, NF-κB and COX-2, which play important roles in inflammation and cancer. S. delavayi Diels. stimulated p38 MApK phosphorylation but reduced NF-κB phosphorylation and COX-2 expression in a dose-and timedependent manner. thus, S. delavayi Diels., which appears to act primarily through p38 MApK/NF-κB/COX-2 signaling in breast carcinomas, may be a potent anticancer agent with target specificity and low toxicity.

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Akt/cAMP-Responsive Element Binding Protein/Cyclin D1 Network: A Novel Target for Prostate Cancer Inhibition in Transgenic Adenocarcinoma of Mouse Prostate Model Mediated by Nexrutine, a Phellodendron Amurense Bark Extract

Cited by 90 publications

References 55 publications

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

Berberine induces cell death in human hepatoma cells in vitro by downregulating CD147

HER-2/neu Mediates Oncogenic Transformation via Altered CREB Expression and Function

Stephania delavayi Diels. inhibits breast carcinoma proliferation through the p38 MAPK/NF-κB/COX-2 pathway

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