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Thyroid carcinogenesis accompanies progressive loss of thyroid-specific differentiated functions. Some thyroid cancers are or become dedifferentiated and they become refractory to efficacy-proven conventional therapies such as radioiodine ablation therapy and TSH-suppressive therapy. Redifferentiation therapy by redifferentiating agent may retard tumor growth and make tumors respond to conventional therapies. Natural polyphenol phytochemicals that can be found in fruit have reported to inhibit cancer initiation, promotion, and progression. And some of these chemicals not only displays in-vitro and in-vivo growth inhibition, but also induces redifferentiation in several types of human cancers. So we examined whether polyphenol phytochemicals could induce antiproliferation and differentiation in F9 embryonal carcinoma cell line (established differentiation model), furthermore whether polyphenol phytochemicals could induce antiproliferation and redifferentiation in thyroid cancer cell lines. In F9 embryonal carcinoma cell line, polyphenol phytochmicals; resveratrol, resorcinol, genistein, quercetin, kaempferol were administered. MTT assay and differentiation assay (laminin B1, tissue plasminogen activator(tPA), collagen type IV RT-PCR) were performed. All of these chemicals dose-dependently decreased tumor proliferation. Of these, resveratrol, genistein, quercetin were more effective and increased differentiation marker laminin B1, tPA, collagen type IV mRNA in F9 cell. In thyroid cancer cell lines; NPA, TPC-1, ARO, FRO, resveratrol, genistein, quercetin dose-dependently decreased tumor proliferation in MTT assay. In NPA, FRO thyroid cancer cell lines, resveratrol, genistein, quercetin decreased expression of dediffenetiation marker CD97 mRNA. Polyphenol phytochemicals; resveratrol, genistein, quercetin induced antiproliferation in TPC-1, NPA, FRO, ARO thyroid cancer cell lines and redifferentiation in NPA, FRO thyroid cancer cell lines. More investigations need to be done to document whether these polyphenol phytochemicals might be effective agents for patients with dedifferentiated thyroid cancers.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]