PMID- 19457706 OWN - NLM STAT- MEDLINE DCOM- 20110316 LR - 20141120 IS - 1879-0593 (Electronic) IS - 1368-8375 (Linking) VI - 45 IP - 10 DP - 2009 Oct TI - Using YC-1 to overcome the radioresistance of hypoxic cancer cells. PG - 915-9 LID - 10.1016/j.oraloncology.2009.04.005 [doi] AB - Targeting hypoxia-inducible factor-1 (HIF-1) active cells in tumors may be an excellent strategy to improve the outcome of radiation therapy. On the basis of the reported role of YC-1 as a HIF-1 inhibitor with anti-cancer activity, we tested the therapeutic efficacy of YC-1 against radioresistance in vitro. The AMC-HN3 cancer cell line, developed from squamous cell carcinoma of the larynx, was cultured under hypoxic conditions or in the presence of cobalt chloride. Both treatments induced nuclear accumulation of HIF-1alpha protein. Cells cultured under normoxic or hypoxic conditions with and without YC-1 treatment were irradiated and analyzed using flow cytometry and clonogenic assays. In the absence of YC-1 treatment, irradiation induced a greater cytotoxic effect in normoxic cells than in cobalt-treated cells. Treatment of cobalt-treated cells with YC-1 effectively inhibited HIF-1alpha expression, and enhanced the sensitivity of cells to radiation, decreasing the surviving fraction to that of normoxic cells. Flow cytometry confirmed these results, showing that the sub-G1 fraction was increased in YC-1-treated hypoxic cells after irradiation. Our results suggest that YC-1 treatment may be an effective therapeutic strategy for overcoming the radioresistance of HIF-1alpha-expressing, hypoxic cancer cells. FAU - Moon, So Young AU - Moon SY AD - Department of Otolaryngology, Asan Medical Center, University of Ulsan College of Medicine, 388-1, Pungnap-dong, Songpa-gu, Seoul 138-736, Republic of Korea. FAU - Chang, Hyo Won AU - Chang HW FAU - Roh, Jong-Lyel AU - Roh JL FAU - Kim, Gui Chull AU - Kim GC FAU - Choi, Seung-Ho AU - Choi SH FAU - Lee, Sang-wook AU - Lee SW FAU - Cho, Kyung-Ja AU - Cho KJ FAU - Nam, Soon Yuhl AU - Nam SY FAU - Kim, Sang Yoon AU - Kim SY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20090519 PL - England TA - Oral Oncol JT - Oral oncology JID - 9709118 RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Indazoles) RN - 0 (Radiation-Sensitizing Agents) RN - 154453-18-6 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole) SB - IM MH - Carcinoma, Squamous Cell/radiotherapy MH - Cell Hypoxia/*drug effects MH - Cell Line, Tumor MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/*antagonists & inhibitors MH - In Vitro Techniques MH - Indazoles/*pharmacology MH - Laryngeal Neoplasms/radiotherapy MH - Radiation Tolerance/*drug effects MH - Radiation-Sensitizing Agents/*pharmacology MH - Treatment Outcome EDAT- 2009/05/22 09:00 MHDA- 2011/03/17 06:00 CRDT- 2009/05/22 09:00 PHST- 2009/03/26 00:00 [received] PHST- 2009/04/14 00:00 [revised] PHST- 2009/04/15 00:00 [accepted] PHST- 2009/05/22 09:00 [entrez] PHST- 2009/05/22 09:00 [pubmed] PHST- 2011/03/17 06:00 [medline] AID - S1368-8375(09)00101-8 [pii] AID - 10.1016/j.oraloncology.2009.04.005 [doi] PST - ppublish SO - Oral Oncol. 2009 Oct;45(10):915-9. doi: 10.1016/j.oraloncology.2009.04.005. Epub 2009 May 19.