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

研究成果: 雜誌貢獻文章同行評審

11 引文 斯高帕斯(Scopus)

摘要

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.
原文英語
頁(從 - 到)17720-17734
頁數15
期刊Molecules
20
發行號10
DOIs
出版狀態已發佈 - 九月 25 2015

ASJC Scopus subject areas

  • 有機化學

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