PMID- 24838151 OWN - NLM STAT- MEDLINE DCOM- 20150909 LR - 20211021 IS - 1532-2807 (Electronic) IS - 1219-4956 (Linking) VI - 21 IP - 1 DP - 2015 Jan TI - Autophagy interplays with apoptosis and cell cycle regulation in the growth inhibiting effect of Trisenox in HEP-2, a laryngeal squamous cancer. PG - 103-11 LID - 10.1007/s12253-014-9794-6 [doi] AB - Laryngeal squamous cell carcinoma (LSCC) is the most common among several types of head and neck cancers. Current treatments have a poor effect on early and advanced cases, and further investigations for novel agents against LSCCs are desirable. In this study, we elucidate the cytotoxic enhancing effect of arsenic trioxide (As2O3) combined with L-buthionine sulfoximine (BSO) in LSCC. The effect of BSO with As2O3 or Cisplatin (CDDP) on cell viability was examined using 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The reactive oxygen species (ROS) levels, cell cycle, and apoptosis were measured by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), propidium iodide (PI) and annexin V/PI. The acidic vacuolar organelles were visualized by fluorescence microscope and quantified using flow cytometry. Neither CDDP nor As2O3 when used alone reduced the cell viability. BSO was found to enhance only As2O3 sensitivity, leading to G2/M arrest and autophagy with no correlation of ROS induction. This result suggests that modulation of glutathione enhances autophagy, which interplays with apoptosis. In this study, we obtained initial preclinical evidence for the potential efficacy of these drugs in a combined therapy protocol. FAU - Pereira, Debora Lima AU - Pereira DL AD - Departamento de Estomatologia, Hospital AC Camargo, Sao Paulo, Brazil. FAU - Dos Santos Ferreira, Ana Carolina AU - Dos Santos Ferreira AC FAU - de Faria, Giselle Pinto AU - de Faria GP FAU - Kwee, Jolie Kiemlian AU - Kwee JK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140518 PL - Switzerland TA - Pathol Oncol Res JT - Pathology oncology research : POR JID - 9706087 RN - 0 (Arsenicals) RN - 0 (Oxides) RN - 0 (Reactive Oxygen Species) RN - Q20Q21Q62J (Cisplatin) RN - S7V92P67HO (Arsenic Trioxide) SB - IM MH - Apoptosis/*drug effects MH - Arsenic Trioxide MH - Arsenicals/*pharmacology MH - Autophagy/*drug effects MH - Carcinoma, Squamous Cell/*drug therapy/metabolism MH - Cell Cycle/*drug effects MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Cisplatin/pharmacology MH - Head and Neck Neoplasms/*drug therapy/metabolism MH - Humans MH - Laryngeal Neoplasms/*drug therapy/metabolism MH - Oxides/*pharmacology MH - Reactive Oxygen Species/metabolism MH - Squamous Cell Carcinoma of Head and Neck EDAT- 2014/05/20 06:00 MHDA- 2015/09/10 06:00 CRDT- 2014/05/20 06:00 PHST- 2013/09/23 00:00 [received] PHST- 2014/05/06 00:00 [accepted] PHST- 2014/05/20 06:00 [entrez] PHST- 2014/05/20 06:00 [pubmed] PHST- 2015/09/10 06:00 [medline] AID - 10.1007/s12253-014-9794-6 [doi] PST - ppublish SO - Pathol Oncol Res. 2015 Jan;21(1):103-11. doi: 10.1007/s12253-014-9794-6. Epub 2014 May 18.