Quercetin suppresses cellular migration and invasion in human head and neck squamous cell carcinoma (HNSCC)
Tóm tắt
Head and neck squamous cell carcinoma (HNSCC) with aberrant epidermal growth factor receptor (EGFR) signaling is often associated with a poor prognosis and a low survival rate. Hence, efficient inhibition of the EGFR signaling-mediated malignancy would improve survival rate. In a previous study, we demonstrated that quercetin appears to be a potent anti-tumorigenic agent through its inhibition of the EGFR/Akt pathway in oral cancer, but its anti-metastatic potential in HNSCC remains unclear [1]. Here, we have hypothesized that quercetin might be effective in metastatic inhibition in EGFR-overexpressing HNSCC cells. Quercetin treatment with 10 μM (half concentration of IC50) suppressed cell migration and invasion in EGFR-overexpressing HSC-3 and FaDu HNSCC cells. Quercetin also inhibited the colony growth of HSC-3 cells embedded in a Matrigel matrix. Among matrix metalloproteinases (MMPs), the secreted gelatinases MMP-2 and MMP-9 are responsible for the degradation of gelatin in the extracellular matrix and type IV collagen in the basement membrane; and this degradation event is crucial for the migration from the origin and the invasion into the bone in HNSCC. Quercetin (10 μM) treatment also suppressed the expression and proteolytic activity of MMP-2 and MMP-9. Taken together, our data indicate that quercetin is an effective anti-cancer agent against MMP-2- and MMP-9-mediated metastasis in EGFR-overexpressing HNSCC.
Tài liệu tham khảo
Huang CY, Chan CY, Chou IT, Lien CH, Hung HC, Lee MF. Quercetin induces growth arrest through activation of FOXO1 transcription factor in EGFR-overexpressing oral cancer cells. J Nutr Biochem 2013, 24(9): 1596-603.
Sheu JJ, Hua CH, Wan L, Lin YJ, Lai MT, Tseng HC, et al. Functional genomic analysis identified epidermal growth factor receptor activation as the most common genetic event in oral squamous cell carcinoma. Cancer research 2009, 69(6):2568-76.
Chung CH, Ely K, McGavran L, Varella-Garcia M, Parker J, Parker N, et al. Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas. J Clin Oncol 2006, 24(25):4170-6.
Temam S, Kawaguchi H, El-Naggar AK, Jelinek J, Tang H, Liu DD, et al. Epidermal growth factor receptor copy number alterations correlate with poor clinical outcome in patients with head and neck squamous cancer. J Clin Oncol 2007, 25(16):2164-70.
Ratushny V, Astsaturov I, Burtness BA, Golemis EA, Silverman JS. Targeting EGFR resistance networks in head and neck cancer. Cell Signal 2009, 21(8): 1255-68.
Modjtahedi H, Essapen S. Epidermal growth factor receptor inhibitors in cancer treatment: advances, challenges and opportunities. Anticancer Drugs 2009, 20(10): 851-5.
Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: mechanisms of activation and signalling. Exp Cell Res 2003, 284(1): 31-53.
Zhou QL, Yang CX, Liang H, Liu HZ, Wang HB, Liu Y, et al. Propofol reduces MMPs expression by inhibiting PI3K/AKT activity in human HepG2 cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2013.
Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. Journal of the National Cancer Institute 1997, 89(17): 1260-70.
Culhaci N, Metin K, Copcu E, Dikicioglu E. Elevated expression of MMP-13 and TIMP-1 in head and neck squamous cell carcinomas may reflect increased tumor invasiveness. BMC cancer 2004, 4: 42.
Komatsu K, Nakanishi Y, Nemoto N, Hori T, Sawada T, Kobayashi M. Expression and quantitative analysis of matrix metalloproteinase- 2 and – 9 in human gliomas. Brain tumor pathology 2004, 21(3):105-12.
Johansson N, Airola K, Grenman R, Kariniemi AL, Saarialho-Kere U, Kahari VM. Expression of collagenase-3 (matrix metalloproteinase- 13) in squamous cell carcinomas of the head and neck. Am J Pathol 1997, 151(2): 499-508.
Kawamata H, Nakashiro K, Uchida D, Harada K, Yoshida H, Sato M. Possible contribution of active MMP2 to lymph-node metastasis and secreted cathepsin L to bone invasion of newly established human oral-squamous-cancer cell lines. Int J Cancer 1997, 70(1): 120-7.
Ruokolainen H, Paakko P, Turpeenniemi-Hujanen T. Serum matrix metalloproteinase-9 in head and neck squamous cell carcinoma is a prognostic marker. Int J Cancer 2005, 116(3): 422-7.
Burtness B. The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Expert Opin Biol Ther 2005, 5(8): 1085-93.
Burtness B, Goldwasser MA, Flood W, Mattar B, Forastiere AA. Phase III randomized trial of cisplatin plus placebo compared with cisplatin plus cetuximab in metastatic/recurrent head and neck cancer: an Eastern Cooperative Oncology Group study. J Clin Oncol 2005, 23(34): 8646-54.
Dobelbower MC, Russo SM, Raisch KP, Seay LL, Clemons LK, Suter S, et al. Epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib, and concurrent 5-fluorouracil, cisplatin and radiotherapy for patients with esophageal cancer: a phase I study. Anticancer Drugs 2006, 17(1): 95-102.
Lamson DW, Brignall MS. Antioxidants and cancer, part 3: quercetin. Altern Med Rev 2000, 5(3): 196-208.
Michaud-Levesque J, Bousquet-Gagnon N, Beliveau R. Quercetin abrogates IL-6/STAT3 signaling and inhibits glioblastoma cell line growth and migration. Exp Cell Res 2012, 318(8): 925-35.
Pan HC, Jiang Q, Yu Y, Mei JP, Cui YK, Zhao WJ. Quercetin promotes cell apoptosis and inhibits the expression of MMP-9 and fibronectin via the AKT and ERK signalling pathways in human glioma cells. Neurochem Int 2015, 80: 60-71.
Cao HH, Cheng CY, Su T, Fu XQ, Guo H, Li T, et al. Quercetin inhibits HGF/c-Met signaling and HGF-stimulated melanoma cell migration and invasion. Mol Cancer 2015, 14: 103.
Bhat FA, Sharmila G, Balakrishnan S, Arunkumar R, Elumalai P, Suganya S, et al. Quercetin reverses EGF-induced epithelial to mesenchymal transition and invasiveness in prostate cancer (PC-3) cell line via EGFR/PI3K/Akt pathway. J Nutr Biochem 2014, 25(11): 1132-9.
Lin CW, Hou WC, Shen SC, Juan SH, Ko CH, Wang LM, et al. Quercetin inhibition of tumor invasion via suppressing PKC delta/ERK/AP-1-dependent matrix metalloproteinase-9 activation in breast carcinoma cells. Carcinogenesis 2008, 29(9): 1807-15.
Seo HS, Ku JM, Choi HS, Choi YK, Woo JK, Kim M, et al. Quercetin induces caspase-dependent extrinsic apoptosis through inhibition of signal transducer and activator of transcription 3 signaling in HER2-overexpressing BT-474 breast cancer cells. Oncol Rep 2016.
Chen SF, Nien S, Wu CH, Liu CL, Chang YC, Lin YS. Reappraisal of the anticancer efficacy of quercetin in oral cancer cells. J Chin Med Assoc 2013, 76(3): 146-52.
Lai WW, Hsu SC, Chueh FS, Chen YY, Yang JS, Lin JP, et al. Quercetin inhibits migration and invasion of SAS human oral cancer cells through inhibition of NF-kappaB and matrix metalloproteinase-2/-9 signaling pathways. Anticancer Res 2013, 33(5):1941-50.
Erdem NF, Carlson ER, Gerard DA, Ichiki AT. Characterization of 3 oral squamous cell carcinoma cell lines with different invasion and/or metastatic potentials. J Oral Maxillofac Surg 2007, 65(9): 1725-33.
Rangan SR. A new human cell line (FaDu) from a hypopharyngeal carcinoma. Cancer 1972, 29(1): 117-21.
Huang CY, Chou YH, Hsieh NT, Chen HH, Lee MF. MED28 regulates MEK1-dependent cellular migration in human breast cancer cells. J Cell Physiol 2012, 227(12): 3820-7.
Lee MF, Chan CY, Hung HC, Chou IT, Yee AS, Huang CY. Nacetylcysteine (NAC) inhibits cell growth by mediating the EGFR/Akt/HMG box-containing protein 1 (HBP1) signaling pathway in invasive oral cancer. Oral Oncol 2012.
Kozaki K, Imoto I, Pimkhaokham A, Hasegawa S, Tsuda H, Omura K, et al. PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. Cancer Sci 2006, 97(12): 1351-8.
Lim SC. Expression of c-erbB receptors, MMPs and VEGF in head and neck squamous cell carcinoma. Biomed Pharmacother 2005, 59 Suppl 2: S366-9.
Ohnishi Y, Lieger O, Attygalla M, Iizuka T, Kakudo K. Effects of epidermal growth factor on the invasion activity of the oral cancer cell lines HSC3 and SAS. Oral Oncol 2008, 44(12): 1155-9.