Somatostatin effects on the proteome of the LNCaP cell-line

Liu, Zhaoxu; Bengtsson, Sofia; Krogh, Morten; Márquez, Marcela; Nilsson, Sten; James, Peter; Aliaya, Ayodele; Holmberg, Anders

doi:10.3892/ijo.30.5.1173

Cited by 16 publications

(19 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, in human malignant melanoma cells, arbutin (hydroquinone-O-beta-D-glucopyranoside), a tyrosinase inhibitor and a potential anti-cancer agent, was found to induce apoptosis by causing VDAC1 over-expression [246,247]. Somatostatin, reported to be useful in the treatment of advanced prostate cancer, was found to up-regulate the expression of VDAC1 and VDAC2 in the LNCaP prostate cancer cell line [248]. Up-regulation of VDAC1 has been reported upon UV irradiation of apoptosis-sensitive cells [249].…”

Section: Apoptosis Stimuli Induce Vdac1 Over-expression -A New Mode Omentioning

confidence: 97%

“…Recently, based on the findings that several cancer drugs and treatments that act by inducing apoptosis lead to up-regulation of VDAC1 expression levels [244][245][246][247][248]254], an additional mode of action for apoptosis stimulus involving increased expression of VDAC1 was proposed [223]. Moreover, it has been argued that apoptosis-inducing agents act by increasing [Ca 2+ ]i and that this in turn leads to an upregulation of VDAC1 expression.…”

Section: Apoptosis Stimuli Induce Vdac1 Over-expression -A New Mode Omentioning

confidence: 98%

See 1 more Smart Citation

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Shoshan‐Barmatz

Ben-Hail

Admoni

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

214

254

View full text Add to dashboard Cite

VDAC1 is found at the crossroads of metabolic and survival pathways. VDAC1 controls metabolic cross-talk between mitochondria and the rest of the cell by allowing the influx and efflux of metabolites, ions, nucleotides, Ca2+ and more. The location of VDAC1 at the outer mitochondrial membrane also enables its interaction with proteins that mediate and regulate the integration of mitochondrial functions with cellular activities. As a transporter of metabolites, VDAC1 contributes to the metabolic phenotype of cancer cells. Indeed, this protein is over-expressed in many cancer types, and silencing of VDAC1 expression induces an inhibition of tumor development. At the same time, along with regulating cellular energy production and metabolism, VDAC1 is involved in the process of mitochondria-mediated apoptosis by mediating the release of apoptotic proteins and interacting with anti-apoptotic proteins. The engagement of VDAC1 in the release of apoptotic proteins located in the inter-membranal space involves VDAC1 oligomerization that mediates the release of cytochrome c and AIF to the cytosol, subsequently leading to apoptotic cell death. Apoptosis can also be regulated by VDAC1, serving as an anchor point for mitochondria-interacting proteins, such as hexokinase (HK), Bcl2 and Bcl-xL, some of which are also highly expressed in many cancers. By binding to VDAC1, HK provides both a metabolic benefit and apoptosis-suppressive capacity that offer the cell a proliferative advantage and increase its resistance to chemotherapy. Thus, these and other functions point to VDAC1 as an excellent target for impairing the re-programed metabolism of cancer cells and their ability to evade apoptosis. Here, we review current evidence pointing to the function of VDAC1 in cell life and death, and highlight these functions in relation to both cancer development and therapy. In addressing the recently solved 3D structures of VDAC1, this review will point to structure-function relationships of VDAC as critical for deciphering how this channel can perform such a variety of roles, all of which are important for cell life and death. Finally, this review will also provide insight into VDAC function in Ca2+ homeostasis, protection against oxidative stress, regulation of apoptosis and involvement in several diseases, as well as its role in the action of different drugs. We will discuss the use of VDAC1-based strategies to attack the altered metabolism and apoptosis of cancer cells. These strategies include specific siRNA able to impair energy and metabolic homeostasis, leading to arrested cancer cell growth and tumor development, as well VDAC1-based peptides that interact with anti-apoptotic proteins to induce apoptosis, thereby overcoming the resistance of cancer cell to chemotherapy. Finally, small molecules targeting VDAC1 can induce apoptosis. VDAC1 can thus be considered as standing at the crossroads between mitochondrial metabolite transport and apoptosis and hence represents an emerging cancer drug target. This article is part of a Special ...

show abstract

Section: Apoptosis Stimuli Induce Vdac1 Over-expression -A New Mode Omentioning

confidence: 97%

Section: Apoptosis Stimuli Induce Vdac1 Over-expression -A New Mode Omentioning

confidence: 98%

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Shoshan‐Barmatz

Ben-Hail

Admoni

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

214

254

View full text Add to dashboard Cite

show abstract

“…PRDX2 mRNA was significantly up-regulated by sms and smsdx treatment in LNCaP cells. PRDX2 protein expression was down-regulated by sms (4). The different manners of regulation by sms/smsdx in PRDXs are thought to be related to phosphorylation, overoxidation and proteolysis of PRDXs.…”

Section: ------------------------------------------------------------mentioning

confidence: 99%

“…Understanding the pathways that lead to AIPC will eventually lead to the development of new therapies. In our previous studies (3,4), smsdx (glycosylated poly sms with high stability suitable for clinical use) was found to be able to trigger upregulation of catalytic mitochondrial proteins and seemed to affect apoptotic-related proteins in androgen-dependent (AD) prostate cancer LNCaP cells. One hypothesis could be that there are groups of proteins crucially involved in the progression and transition to HRPC.…”

Section: Introductionmentioning

confidence: 99%

Comparison of protein expression in two prostate cancer cell-lines, LNCaP and DU145, after treatment with somatostatin

Liu

Márquez²,

Nilsson³

et al. 2009

Oncol Rep

View full text Add to dashboard Cite

Abstract. The mechanisms underlying prostate cancer progression are poorly understood. Proteins responsive to androgens may be involved in the development and progression of prostate cancer and the ultimate failure of androgen-ablation therapy. Therapy with somatostatin (sms) analogues could be a possible therapeutic alternative to chemotherapy in hormone refractory prostate cancer patients. We used two prostate cancer cell-lines, LNCaP (androgendependent) and DU145 (androgen-independent), to compare the protein expressions. Both cell lines were treated with sms and its derivative smsdx. Smsdx is a glycosylated poly sms with high stability suitable for clinical use. A comparison study of protein expression was analyzed by means of twodimensional gel electrophoresis (2DE) followed by mass spectrometric analysis. Marked quantitative differences were observed in the protein expression profiles in sms/smsdx treated LNCaP and DU145 cells compared to the control cells. One third of the detected proteins were differentially expressed (PRDXs, hnRNPs, HSPs, RKIP). Concordance in protein expression patterns was observed between smsdx and sms treated cells with strong agreement between the up-and down-regulation of proteins. Fifty-eight (isoforms of 49 proteins) protein spots were identified and found differentially expressed at 2-fold change between LNCaP and DU145 cells. Thirty-one proteins in LNCaP have higher expressions than in DU145. Twenty-seven proteins in DU145 have higher expressions than in LNCaP. Most of the differentially expressed proteins (2-fold) between LNCaP and DU145 cells were affected by sms/smsdx treatment (1.2-to 2.6-fold change). Sms/smsdx affects the mitochondria of prostate cancer cells in a way that eventually triggers mitochondrialmediated apoptosis. Regulation of certain proteins (e.g., RKIP, VDACs) by sms/smsdx suggests that sms/smsdx exerts its effects on prostate cancer cells via MAPK pathway and by regulating the activities of phosphotyrosine phosphatases. IntroductionProstate cancer is the most common malignancy and the second leading cause of cancer-related mortality in men in the Western world (1). Although androgen ablation is the most effective therapy for patients with advanced prostate cancer, progression to androgen independence (AIPC) and hormone refractory (HRPC) eventually occurs (2). Androgenindependent prostate cancer carries a bleak prognosis with short survival time. AIPC metastasizes preferentially to the skeleton which is associated with considerable morbidity such as pain and fractures.Several pathways provide insights into the mechanism of androgen action and schemes by which cancer cells subvert normal growth control and escape treatment attempts. Understanding the pathways that lead to AIPC will eventually lead to the development of new therapies. In our previous studies (3,4), smsdx (glycosylated poly sms with high stability suitable for clinical use) was found to be able to trigger upregulation of catalytic mitochondrial proteins and seemed to affect apoptotic-related...

show abstract

“…The lymph node cancerous prostate (LNCaP) cell line under somatostatin upregulated VDAC here probably a factor curbing the progression to hormone-refractory prostate cancer. 3 LNCaP cells on their way to NE-differentiation increased IClswell based RVD, and also endogenous chloride channel-3 (ClC-3), 4 a candidate to modulate VRAC. Taking for granted that VRAC complexes as IClswell effectors are VDAC-cored , its expression level had to follow, or vice versa.…”

mentioning

confidence: 99%

Author's Reply to Letter to the Editor to Enhanced VDAC‐cored VRAC in NE‐LNCaP cells points to an involvement of eukaryotic porin in the extrinsic apoptotic pathway (Author's Reply)

Komiya

Suzuki

2009

Int J of Urology

View full text Add to dashboard Cite

A synopsis of recent literature insinuates a closer look at type-1 voltage-dependent anion channels (VDAC)-cored volume-regulated anion channel (VRAC) complexes in studies on the neuroendocrine (NE)-differentiation of cancerous cells.Cell membrane-standing type-1 VDAC is involved in the regulatory volume decrease (RVD) of cells via VDAC-cored VRAC complexes, carrying IClswell.1 Type-1 VDAC in cell membranes of neurons supports staurosporine-induced apoptosis as part of the apoptotic volume decrease (AVD) pathway, 2 thus pointing to an identity with VRAC (http://www.futhin.de). The lymph node cancerous prostate (LNCaP) cell line under somatostatin upregulated VDAC here probably a factor curbing the progression to hormone-refractory prostate cancer. 3LNCaP cells on their way to NE-differentiation increased IClswell based RVD, and also endogenous chloride channel-3 (ClC-3), 4 a candidate to modulate VRAC. Taking for granted that VRAC complexes as IClswell effectors are VDAC-cored , its expression level had to follow, or vice versa. Cell volume regulation as well as apoptosis of cells can be blocked by VRAC blockers; 1,2 correspondingly basic or enhanced RVD of the LNCaP cell lines studied were equally inhibited by 5-nito-2-(3-phenylpropylamino) benzoic acid (NPPB); 4 crtl-LNCaP cells under the SERCA pump inhibitor thapsigargin and calcium showed about 50% IClswell reduction, while NE-LNCaP cells were almost unaffected with 3%, indicating the involvement of store-operated calcium channel (SOC) regulation in the differing phenotypes. 4 However, under the stimulus of tumor necrosis factor (TNF)-a in normotonic surroundings, the ctrl-LNCaP line, carrying less VRAC, showed a higher rate of inducible apoptosis as did its NE-differentiated form, 4 which, furthermore, as a surprise, in either cell line further increased when the established IClswell current = VRAC blocker NPPB was added to the setting. A paradox appears: while on the one hand , anti-VDAC antibodies block staurosporine-induced apoptosis of neuronal cells by blocking VDAC-cored AVD, on the other hand , the RVD-blocker NPPB enhances the apoptotic rate of either LNCaP cell line under the apoptotic stimulus of TNFa. Anyway, intriguing questions arise, such as which one of the established apoptotic pathways is affected in the issue? Author's Replyi ju_2334 702Author's Reply to Letter to the Editor to Enhanced VDAC-cored VRAC in NE-LNCaP cells points to an involvement of eukaryotic porin in the extrinsic apoptotic pathwayThank you very much for your letter entitled 'Enhanced VDAC-cored VRAC in NE-LNCaP cells points to an involvement of eukaryotic porin in the extrinsic apoptotic pathway'. Our previous review article published in IJU demonstrated the clinical importance of neuroendocrine (NE) cell proliferation in an androgen-independent manner.1 Also, we suggested that NE cells can be potential therapeutic targets for hormone-refractory prostate cancer (HRPC) patients.Thinnes et al. have reported voltage-dependent anion channels (VDAC)-related pathway involvemen...

show abstract

Somatostatin effects on the proteome of the LNCaP cell-line

Cited by 16 publications

References 38 publications

The mitochondrial voltage-dependent anion channel 1 in tumor cells

The mitochondrial voltage-dependent anion channel 1 in tumor cells

Comparison of protein expression in two prostate cancer cell-lines, LNCaP and DU145, after treatment with somatostatin

Author's Reply to Letter to the Editor to Enhanced VDAC‐cored VRAC in NE‐LNCaP cells points to an involvement of eukaryotic porin in the extrinsic apoptotic pathway (Author's Reply)

Contact Info

Product

Resources

About