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- Title
Autophagy Interplays with Apoptosis and Cell Cycle Regulation in the Growth Inhibiting Effect of Trisenox in HEP-2, a Laryngeal Squamous Cancer.
- Authors
Pereira, Débora; Santos Ferreira, Ana; Faria, Giselle; Kwee, Jolie
- Abstract
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 (AsO) combined with L-buthionine sulfoximine (BSO) in LSCC. The effect of BSO with AsO 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 AsO when used alone reduced the cell viability. BSO was found to enhance only AsO 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.
- Subjects
LARYNGEAL cancer; SQUAMOUS cell carcinoma; ARSENIC trioxide; SULFOXIMINES; AUTOPHAGY; APOPTOSIS; CISPLATIN; CELL cycle regulation; PHYSIOLOGY; THERAPEUTICS
- Publication
Pathology & Oncology Research, 2015, Vol 21, Issue 1, p103
- ISSN
1219-4956
- Publication type
Article
- DOI
10.1007/s12253-014-9794-6