2-(3-Methoxyphenyl)-6,7-methylenedioxoquinolin-4-one,a novel synthetic compound,inhibited migration and invasion in TSGH8301 human bladder cancer cells

Abstract

Matrix metalloproteinases (MMPs) play an important role in the invasion, metastasis and angiogenesis of cancer cells. Many agents have been shown to inhibit the cancer cell migration and invasion by suppression of MMPs. 2-(3-Methoxyphenyl)-6,7-methylenedioxoquinolin-4-one (MMEQ) is a derivative compound synthesized from quinolin and the purpose of this study is to determine whether or not cell migration would be reduced in human bladder cancer TSGH8301 cells after MMEQ treatment. Wound healing assay and boyden chamber assay were used in cell migration and invasion determinations. Cell migration and invasion inhibited by MMEQ exerted an inhibitory effect on the sevenless homolog-1 (SOS-1), protein kinase c (PKC), extracellular signal-regulated kinase (ERK) and Rho A for causing the inhibitions of MMP-2 and -9, and then followed by the inhibitions of invasion and migration. MMEQ also affected FAK, PI3K or inhibited growth factor receptor-bound protein 2 (GRB2), nuclear factor kappaB (NF-κB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) for cell proliferation inhibition. Therefore, MMEQ may serve as a drug in the prevention of tumor metastasis of bladder cancer in the future.

Keywords

2-(3-methoxyphenyl)-6 7-methylenedioxoquinolin-4-one (MMEQ)cell migration cell invasion TSGH8301 human bladder cancer cells

References

Woodhouse EC , Chuaqui RF , and Liotta LA General mechanisms of metastasis. Cancer 1997; 80: 1529- 1537.

Chen YL , Fang KC , Sheu JY , Hsu SL , and Tzeng CC Synthesis and antibacterial evaluation of certain quinolone derivatives. J Med Chem 2001; 44: 2374-2377.

Hsu SC , Lu JH , Kuo CL , et al. Crude extracts of Solanum lyratum induced cytotoxicity and apoptosis in a human colon adenocarcinoma cell line (colo 205). Anticancer Res 2008; 28: 1045-1054.

Hsu SC , Kuo CL , Lin JP , et al. Crude extracts of Euchresta formosana radix inhibit invasion and migration of human hepatocellular carcinoma cells. Anticancer Res 2007; 27: 2377-2384.

Fishman DA , Liu Y. , Ellerbroek SM , and Stack MS Lysophosphatidic acid promotes matrix metalloproteinase (MMP) activation and MMP-dependent invasion in ovarian cancer cells. Cancer Res 2001; 61: 3194-3199.

Lin SS , Lai KC , Hsu SC , et al. Curcumin inhibits the migration and invasion of human A549 lung cancer cells through the inhibition of matrix metalloproteinase-2 and -9 and Vascular Endothelial Growth Factor (VEGF). Cancer Lett 2009; 285: 127-133.

Ho YT , Yang JS , Li TC , et al. Berberine suppresses in vitro migration and invasion of human SCC-4 tongue squamous cancer cells through the inhibitions of FAK, IKK, NF-kappaB, u-PA and MMP-2 and -9. Cancer Lett 2009; 279: 155-162.

Pilcher BK , Dumin JA , Sudbeck BD , Krane SM , Welgus HG , and Parks WC The activity of collagenase-1 is required for keratinocyte migration on a type I collagen matrix. J Cell Biol 1997; 137: 1445-1457.

Huang YT , Hwang JJ , Lee LT , et al. Inhibitory effects of a luteinizing hormone-releasing hormone agonist on basal and epidermal growth factor-induced cell proliferation and metastasis-associated properties in human epidermoid carcinoma A431 cells . Int J Cancer 2002; 99: 505-513.

10.

Anand-Apte B. , Zetter B. Signaling mechanisms in growth factor-stimulated cell motility. Stem Cells 1997; 15: 259-267.

11.

Price JT , Thompson EW Mechanisms of tumour invasion and metastasis: emerging targets for therapy . Expert Opin Ther Targets 2002; 6: 217-233.

12.

Fenteany G. , Zhu S. Small-molecule inhibitors of actin dynamics and cell motility. Curr Top Med Chem 2003; 3: 593-616.

13.

Hidalgo M. , Eckhardt SG Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst 2001; 93: 178-193.

14.

Ende C. , Gebhardt R. Inhibition of matrix metalloproteinase-2 and -9 activities by selected flavonoids . Planta Med 2004; 70: 1006-1008.

15.

Karna E. , Palka JA Inhibitory effect of acetylsalicylic acid on metalloproteinase activity in human lung adenocarcinoma at different stages of differentiation. Eur J Pharmacol 2002; 443: 1-6.