PURPOSE: Recently, it has been reported that angiotensin-I converting enzyme (ACE) inhibitors have anticancer activity. In particular, the ACE inhibitor, perindopril, significantly inhibits tumor growth and angiogenesis in hepatocellular carcinoma cells along with suppression of the VEGF level. However, the mechanisms of suppression of the VEGF level are still unclear, and there are no previous reports on this subject related to head and neck squamous cell carcinoma (HNSCC). In some previous studies, angiotensin II, which is produced from angiotensin I by ACE, directly stimulates VEGF expression. METHODS: In the present study, we focused upon angiotensin II, and investigated the effect of perindopril on VEGF expression, angiogenesis, and tumor development of HNSCC with in vitro and in vivo studies. RESULTS: In the in vitro cell proliferation assays, there was no significant difference between the perindopril-treated group and the control group. However, the perindoprilat-treated group showed a significant reduction in mRNA expression of VEGF and inhibited the induction activity of the VEGF promoter in comparison to the control group. Perindoprilat treatment also significantly suppressed angiotensin II production in vitro. In the in vivo studies, perindopril had a significant inhibitory effect on tumor growth, and reduced blood vessel formation surrounding the tumors. CONCLUSIONS: Our findings suggest that perindopril has no direct cytotoxicity against tumor cells, but has a potential to inhibit tumor growth due to suppression of VEGF-induced angiogenesis in vivo. Angiotensin II might have an important role in carcinogenesis, and the antiangiogenic activity of perindopril is at least partly mediated by angiotensin II inhibition. The ACE inhibitor perindopril has clinical potential as a useful antitumor agent.
PURPOSE: Recently, it has been reported that angiotensin-I converting enzyme (ACE) inhibitors have anticancer activity. In particular, the ACE inhibitor, perindopril, significantly inhibits tumor growth and angiogenesis in hepatocellular carcinoma cells along with suppression of the VEGF level. However, the mechanisms of suppression of the VEGF level are still unclear, and there are no previous reports on this subject related to head and neck squamous cell carcinoma (HNSCC). In some previous studies, angiotensin II, which is produced from angiotensin I by ACE, directly stimulates VEGF expression. METHODS: In the present study, we focused upon angiotensin II, and investigated the effect of perindopril on VEGF expression, angiogenesis, and tumor development of HNSCC with in vitro and in vivo studies. RESULTS: In the in vitro cell proliferation assays, there was no significant difference between the perindopril-treated group and the control group. However, the perindoprilat-treated group showed a significant reduction in mRNA expression of VEGF and inhibited the induction activity of the VEGF promoter in comparison to the control group. Perindoprilat treatment also significantly suppressed angiotensin II production in vitro. In the in vivo studies, perindopril had a significant inhibitory effect on tumor growth, and reduced blood vessel formation surrounding the tumors. CONCLUSIONS: Our findings suggest that perindopril has no direct cytotoxicity against tumor cells, but has a potential to inhibit tumor growth due to suppression of VEGF-induced angiogenesis in vivo. Angiotensin II might have an important role in carcinogenesis, and the antiangiogenic activity of perindopril is at least partly mediated by angiotensin II inhibition. The ACE inhibitor perindopril has clinical potential as a useful antitumor agent.
Authors: O V Volpert; W F Ward; M W Lingen; L Chesler; D B Solt; M D Johnson; A Molteni; P J Polverini; N P Bouck Journal: J Clin Invest Date: 1996-08-01 Impact factor: 14.808
Authors: H Yoshiji; S Kuriyama; M Kawata; J Yoshii; Y Ikenaka; R Noguchi; T Nakatani; H Tsujinoue; H Fukui Journal: Clin Cancer Res Date: 2001-04 Impact factor: 12.531
Authors: June Yun; Petra Rocic; Yuh Fen Pung; Souad Belmadani; Ana Catarina Ribeiro Carrao; Vahagn Ohanyan; William M Chilian Journal: Antioxid Redox Signal Date: 2009-08 Impact factor: 8.401
Authors: Jaclyn H Neo; Eleanor I Ager; Peter W Angus; Jin Zhu; Chandana B Herath; Christopher Christophi Journal: BMC Cancer Date: 2010-04-10 Impact factor: 4.430
Authors: Zachary S Morris; Sandeep Saha; William J Magnuson; Brett A Morris; Jenna F Borkenhagen; Alisa Ching; Gayle Hirose; Vanesa McMurry; David M Francis; Paul M Harari; Rick Chappell; Stuart Tsuji; Mark A Ritter Journal: Cancer Date: 2016-05-20 Impact factor: 6.860
Authors: Stefan Wilop; Sabine von Hobe; Martina Crysandt; Albert Esser; Rainhardt Osieka; Edgar Jost Journal: J Cancer Res Clin Oncol Date: 2009-04-28 Impact factor: 4.553
Authors: Nicole M Fischer; Tim O Nieuwenhuis; Bhuchitra Singh; Gayane Yenokyan; James H Segars Journal: J Clin Endocrinol Metab Date: 2021-01-23 Impact factor: 5.958
Authors: Richard E Kast; John A Boockvar; Ansgar Brüning; Francesco Cappello; Wen-Wei Chang; Boris Cvek; Q Ping Dou; Alfonso Duenas-Gonzalez; Thomas Efferth; Daniele Focosi; Seyed H Ghaffari; Georg Karpel-Massler; Kirsi Ketola; Alireza Khoshnevisan; Daniel Keizman; Nicolas Magné; Christine Marosi; Kerrie McDonald; Miguel Muñoz; Ameya Paranjpe; Mohammad H Pourgholami; Iacopo Sardi; Avishay Sella; Kalkunte S Srivenugopal; Marco Tuccori; Weiguang Wang; Christian R Wirtz; Marc-Eric Halatsch Journal: Oncotarget Date: 2013-04