Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer

Kosaka, Takeo; Miyajima, Akira; Takayama, Eiji; Kikuchi, Eiji; Nakashima, Jun; Ohigashi, Takashi; Asano, Tomohiko; Sakamoto, Michiie; Okita, Hajime; Murai, Masaru; Hayakawa, Masamichi

doi:10.1002/pros.20486

Cited by 92 publications

(104 citation statements)

References 33 publications

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“…Thus, there may be a potential beneficial role of AT2R in cancer, and this idea is supported by data that indicate that pheochromocytoma growth is inhibited by AT2R activation (19). With regard to the prostate, there is clear evidence of a tissue-based renin-angiotensin system within this gland and studies to date indicate beneficial actions of blocking AT1R and activating AT2R (15,(20)(21)(22)(23). For example, AT1R inhibitors decrease the growth of some prostate cancer cell lines and delay the development of prostate cancer, whereas AT2R inhibitors are present and have the ability to inhibit epidermal growth factor-induced prostate cancer cell growth in LNCaP and fast-growing androgen-independent PC3 cell lines (24).…”

Section: Introductionmentioning

confidence: 89%

Angiotensin type 2 receptor–mediated apoptosis of human prostate cancer cells

et al. 2009

Molecular Cancer Therapeutics

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Angiotensin II (Ang II) type 1 receptor blocking drugs have been shown to inhibit the growth of prostate cancer cells and delay the development of prostate cancer. Functional Ang II type 2 receptors (AT2R) are present in these cells and inhibit growth induced by epidermal growth factor. The present studies report apoptosis of prostate cancer cells induced by AT2R overexpression. A recombinant adenoviral vector expressing AT2R (Ad-G-AT2R-EGFP) was transduced into prostate cancer cells, including androgen-independent (DU145 and PC3) and androgen-dependent cell lines (LNCaP). Following AT2R transduction, apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining and caspase-3 activity assays. The results indicate that increased expression of AT2R alone induced apoptosis in the prostate cancer lines, an effect that did not require Ang II. AT2R overexpression in DU145 cells induced inhibition of proliferation, a significant reduction of S-phase cells, and an enrichment of G 1 -phase cells. The data also indicate that overexpression of AT2R led to apoptosis via an extrinsic cell death signaling pathway that is dependent on activation of p38 mitogen-activated protein kinase, caspase-8, and caspase-3. Finally, the apoptosis induced by AT2R over-

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Section: Introductionmentioning

confidence: 89%

Angiotensin type 2 receptor–mediated apoptosis of human prostate cancer cells

et al. 2009

Molecular Cancer Therapeutics

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“…[23][24][25] Primary antibody (polyclonal anti-TS antibody and monoclonal anti-Ki67 antibody at a dilution of 1:250) was applied, and they were incubated with secondary antibodies conjugated to peroxidase-labeled dextran polymer. Visualization of the immunoreaction was performed with diaminobenzidine (DAB).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Low‐dose docetaxel enhances the sensitivity of S‐1 in a xenograft model of human castration resistant prostate cancer

Hasegawa¹,

Miyajima²,

Kosaka³

et al. 2011

Intl Journal of Cancer

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S-1 is a recently developed dihydropyrimidine dehydrogenase inhibitor fluoropyrimidine and has demonstrated high maximum plasma 5-Fluorouracil (5-FU) levels with mild toxicity, and an oral formulation has resulted in an improvement in patient quality of life. The aims of the present study were to determine the efficacy of S-1 or S-1 combined with docetaxel (DOC) using castration resistant prostate cancer (CRPC) cells and to explore their clinical potential for treating CRPC patients. LNCaP cells, androgen dependent prostate cancer (ADPC) cells and C4-2 cells, which are a CRPC subline of LNCaP cells, were used. Specimens obtained from ADPC and CRPC patients were also evaluated. The CRPC specimens and C4-2 cells exhibited significantly lower thymidylate synthase (TS) expression, a target of 5-FU, than the ADPC specimens and LNCaP cells. In vitro, C4-2 cells exhibited higher sensitivity to 5-FU than LNCaP cells. In C4-2 xenograft model, S-1 monotherapy suppressed tumor growth and low-dose DOC enhanced the anti-tumor effect of S-1. In vitro, low-dose DOC, which did not induce G2/M arrest, increased p53 and p21 and resulted in down-regulation of TS in C4-2 cells, and down-regulation of TS is considered to be responsible for the synergistic effect of S-1 in vivo. The present findings indicate that CRPC patients with androgen ablation may be good candidates for 5-FU based chemotherapy, and these regimens have attractive therapeutic potential for clinical practice, and they may have a significant impact on therapeutic options.

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“…However, a number of reports exist on the concept of a localized RAS (tissue RAS) in various tissues. Angiotensin II type 1 (AT1) receptor has been also detected in carcinomas of the larynx, lung, liver, pancreas, kidney, bladder, prostate gland, breast, ovary, cervix, in malignant melanoma, and in sarcomas (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Lever et al reported the first clinical evidence that a long-term angiotensin II blockade might have a protective effect against carcinogenesis (17).…”

Section: Introductionmentioning

confidence: 99%

“…Lever et al reported the first clinical evidence that a long-term angiotensin II blockade might have a protective effect against carcinogenesis (17). There is increasing evidence that angiotensin II is involved in tumor biology and the potential anti-tumor effect of angiotensin II type 1 (AT1) receptor antagonist in tumors expressing AT1 receptor (8)(9)(10)(11)(12)(13)(14)(15)(16). Hence, the blockade of angiotensin II has been considered a noteworthy molecular targeted therapy in recent years.…”

Section: Introductionmentioning

confidence: 99%

Local angiotensin II-generation in human gastric cancer: Correlation with tumor progression through the activation of ERK1/2, NF-κB and survivin

Koyama

Fushida²,

Harada³

et al. 2009

Int J Oncol

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Abstract. Angiotensin II is a main effector peptide in renin-angiotensin system, acting as a growth promoter via angiotensin II type 1 (AT1) receptor. The present study examined intrinsic angiotensin II generating system in gastric cancer and potential roles of angiotensin II in cellular proliferation and survival. The expression of AT1 receptor was examined in gastric cancer cell lines and tissues. In addition, we measured angiotensin II concentration in tissues from twenty gastric cancer and corresponding normal region using the florisil method. In vitro, we investigated the potential roles of angiotensin II in cellular proliferation and cell survival in cultured human gastric cancer cell line. The effects of AT1 receptor blocker candesartan were evaluated in a mouse model of peritoneal carcinomatosis. AT1 receptor protein was expressed in gastric cancer cell lines and tissues. Angiotensin II concentration in tumor region (1447±624 pg/g wet) was significantly higher than those of normal region (775±320 pg/g wet) (p<0.05). Angiotensin II stimulates the cell proliferation in the AT1 receptor-positive OCUM2MD3 gastric cancer cell line and this proliferative effect of angiotensin II was inhibited by a specific AT1 receptor antagonist, candesartan. We also confirmed the angiotensin II stimulated ERK1/2, nuclear transcript factor-κB (NF-κB) and surviving activation, which are central molecules of cellular proliferation and survival in OCUM2MD3 cells. Candesartan significantly prolonged survival time in a mouse model of peritoneal carcinomatosis compared with control group (p=0.0.197, log-rank test). Our data provide in vivo evidence of intrinsic angiotensin II generating system in gastric cancer and indicate locally formed angiotensin II is involved in cellular proliferation and survival.

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Angiotensin II type 1 receptor antagonist as an angiogenic inhibitor in prostate cancer

Abstract: Candesartan exerted preventive effects on HRPC, rather than on androgen-sensitive PCa, through the inhibition of tumor angiogenesis.

Cited by 92 publications

References 33 publications

Angiotensin type 2 receptor–mediated apoptosis of human prostate cancer cells

Angiotensin type 2 receptor–mediated apoptosis of human prostate cancer cells

Low‐dose docetaxel enhances the sensitivity of S‐1 in a xenograft model of human castration resistant prostate cancer

Local angiotensin II-generation in human gastric cancer: Correlation with tumor progression through the activation of ERK1/2, NF-κB and survivin

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