Anticancer effects of Hinokitiol: The pivotal role on inhibiting MMPs 2 and 9 and modulating antioxidant enzymes in mouse melanoma cells
Thanasekaran Jayakumar, Chien-Hsun Huang and Joen-Rong Sheu
Taipei Medical University, Taiwan
: Forensic Toxicol Pharmacol 2015, 4:3
Abstract
Numerous reports have been shown that inhibition of matrix metalloproteinases (MMP) expression and/or inhibition of their enzyme activities can be used as early targets for preventing cancer metastasis. MMP-2 (72-kDa gelatinase A) and MMP-9 (92- kDa gelatinase B) are involved in the invasive metastatic potential of tumor cells. Number of recent evidence has revealed that natural dietary antioxidants are capable of inhibiting cancer cell growth. Moreover, these natural antioxidants are reported to have the ability to enhance the activities of detoxification enzymes. Decrease in the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) noted in tumor group is regarded as markers of malignant transformation. Therefore the significant elevation of SOD and CAT may be the potential targets for anticancer therapy. Thus, great attention is focused on developing agents or drugs that can inhibit metastasis via inhibiting MMPs and modulating antioxidant defense. Hinokitiol, a natural bioactive compound found in Chamacyparis taiwanensis , has long been used in hair tonics, cosmetics, and food as an antimicrobial agent. In this study, it appeared to achieve hinokitiol reduces the expression of MMP-2 and 9 by suppressing the phosphorylation of mitogen- activated protein kinase (MAPK) signaling molecules followed by inhibiting the phosphorylation of p65 nuclear factor kappa B (NFκ-B) in melanoma (B16-F10) cells. In addition, hinokitiol increased the activities of CAT and SOD detected by native polyacrylamide gel electrophoresis in this cell. Moreover, electron spins resonance (ESR) study shown that hinokitiol suppressed hydroxyl radical (OH°) formation in a concentration dependent manner. These findings suggest that hinokitiol holds a potent anticancer effect via inhibiting MMPs 2 and 9, modulating antioxidant defense and suppressing OH° formation in B16-F10 melanoma cells. These results may accelerate the development of novel therapeutic agents for the treatment of malignant cancers.
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