Suppressing effect of resveratrol on the migration and invasion of human metastatic lung and cervical cancer cells

• Published in: Molecular biology reports Vol. 39; no. 9; pp. 8709 - 8716
• Main Authors: Kim, Yoon Suk, Sull, Jae Woong, Sung, Ho Joong
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-09-2012; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Antineoplastic Agents, Phytogenic - pharmacology; Biomedical and Life Sciences; Cell division; Cell Line, Tumor; Cell Movement - drug effects; Cell Survival - drug effects; Cervical cancer; Drug therapy; Female; HeLa Cells; Histology; Humans; Life Sciences; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Morphology; Neoplasm Metastasis; NF-kappa B - genetics; NF-kappa B - metabolism; Reactive Oxygen Species - metabolism; Stilbenes - pharmacology; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Transcriptional Activation; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; MMP-9; Lung cancer; Cell migration; Invasion; Cervical cancer; Resveratrol
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-012-1728-3

The antioxidant 3,4′,5 tri-hydroxystilbene (resveratrol), a phytoalexin found in grapes, shows cancer preventive activities, including inhibition of migration and invasion of metastatic tumors. However, the molecular mechanism underlying the effect of resveratrol on tumor metastasis, especially in human metastatic lung and cervical cancers is not clear. A non-cytotoxic dosage of resveratrol causes a reduction in the generation of reactive oxygen species, and suppresses phorbol 12-myristate 13-acetate (PMA)-induced invasion and migration in both A549 and HeLa cells. Resveratrol also decreases both the expression and the enzymatic activity of matrix metalloproteinase-9 (MMP-9), and the promoter activity of PMA-stimulated MMP-9 is also inhibited. However, resveratrol does not affect either the expression or the proteolytic activity of MMP-2. Our results also show that resveratrol suppresses the transcription of MMP-9 by the inhibition of both NF-κB and AP-1 transactivation. These results indicate that resveratrol inhibits both NF-κB and AP-1 mediated MMP-9 expression, leading to suppression of migration and invasion of human metastatic lung and cervical cancer cells. Resveratrol has potential for clinical use in preventing invasion by human metastatic lung and cervical cancers.