Hinokitiol exerts anticancer activity through downregulation of MMPs 9/2 and enhancement of catalase and SOD enzymes: In vivo augmentation of lung histoarchitecture

Chien Hsun Huang, Thanasekaran Jayakumar, Chao Chien Chang, Tsorng Harn Fong, Shing Hwa Lu, Philip Aloysius Thomas, Cheuk-Sing Choy, Joen Rong Sheu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Melanoma is extremely resistant to chemotherapy and the death rate is increasing hastily worldwide. Extracellular matrix promotes the migration and invasion of tumor cells through the production of matrix metalloproteinase (MMP)-2 and -9. Evidence has shown that natural dietary antioxidants are capable of inhibiting cancer cell growth. Our recent studies showed that hinokitiol, a natural bioactive compound, inhibited vascular smooth muscle cell proliferation and platelets aggregation. The present study is to investigate the anticancer efficacy of hinokitiol against B16-F10 melanoma cells via modulating tumor invasion factors MMPs, antioxidant enzymes in vitro. An in vivo mice model of histological investigation was performed to study the patterns of elastic and collagen fibers. Hinokitiol inhibited the expression and activity of MMPs-2 and -9 in B16-F10 melanoma cells, as measured by western blotting and gelatin zymography, respectively. An observed increase in protein expression of MMPs 2/9 in melanoma cells was significantly inhibited by hinokitiol. Notably, hinokitiol (1-5 μM) increased the activities of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD) from the reduction in melanoma cells. Also, hinokitiol (2-10 μM) concentration dependently reduced in vitro Fenton reaction induced hydroxyl radical (OH·) formation. An in vivo study showed that hinokitiol treatment increased elastic fibers (EF), collagens dispersion, and improved alveolar alterations in the lungs of B16/F10 injected mice. Overall, our findings propose that hinokitiol may be a potent anticancer candidate through down regulation of MMPs 9/2, reduction of OH· production and enhancement of antioxidant enzymes SOD and CAT.

Original languageEnglish
Pages (from-to)17720-17734
Number of pages15
JournalMolecules
Volume20
Issue number10
DOIs
Publication statusPublished - Sep 25 2015

Keywords

  • Antioxidant enzymes
  • Elastic fiber
  • Hinokitiol
  • Histology
  • Melanoma
  • MMPs

ASJC Scopus subject areas

  • Organic Chemistry

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