2. Academic Validation
  3. NO-dependent attenuation of TPA-induced immunoinflammatory skin changes in Balb/c mice by pindolol, heptaminol or ATRA, but not by verapamil

NO-dependent attenuation of TPA-induced immunoinflammatory skin changes in Balb/c mice by pindolol, heptaminol or ATRA, but not by verapamil

  • Oncotarget. 2016 Jul 26;7(30):47576-47585. doi: 10.18632/oncotarget.10217.
Jinhyuk F Chung 1,  Calvin J Yoon 2,  Seon Ah Cheon 3,  Eun Seok Seo 2 4,  Sung Ho Park 4,  Jae Seung Yang 5,  Bumju Kim 2,  Min Young Joo 3,  Tae Jung Park 3,  Ki Hean Kim 2,  Anil K Sood 6,  Sang Joon Lee 2 4
Affiliations

Affiliations

  • 1 Synergy Point Co., Sungnam, South Korea.
  • 2 Division of Integrative Biosciences and Biotechnology (IBB), Pohang University of Science and Technology (POSTECH), Pohang, South Korea.
  • 3 NanoBio-Chemistry Laboratory, Department of Chemistry, Chung-Ang University, Seoul, South Korea.
  • 4 Center for Biofluid and Biomimic Research, Department of Mechanical Engineering, Pohang University of Science and Technology (POSTECH), Pohang, South Korea.
  • 5 Clinical Immunology, Laboratory Science Unit, International Vaccine Institute, Seoul, South Korea.
  • 6 Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
PMID: 27374093 DOI: 10.18632/oncotarget.10217
Abstract

Recently a mouse skin carcinogenesis study reported that a β-blocker carvedilol displayed antitumor-properties via antihyperplastic effects. However, the antihyperplastic mechanism is unclear as the β-blocker is characterized with multiple pleiotropic effects including stimulation of endothelial NO release and verapamil-like Calcium Channel blocking activity. To investigate the nature and the origin of the antihyperplastic effects, we tested topical pretreatment with pindolol, heptaminol, ATRA or verapamil against Balb/c mouse ear skin hyperplasia that was induced by TPA. We found that pindolol, heptaminol or ATRA, but not verapamil, inhibited the TPA-induced immunoinflammatory skin changes in an NO-dependent manner, which included epidermal hyperplasia, skin edema and fibrosis. Furthermore, we also observed NO-dependent alleviation of the TPA-induced NK cell depletion in the ear tissues by heptaminol pretreatment. Together our results suggest that stimulation of NO generation from constitutive synthases may be primarily responsible for the reported antihyperplastic and NK cell-preserving effects of the β-blockers, and that similar effects may be observed in other immunity normalizing compounds that also promote endothelial NO synthesis.

Keywords

beta-blocker; heptaminol; nitric oxide; phorbol; tumor promotion.

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