Pathology & Oncology Research

, Volume 21, Issue 1, pp 103-111

First online:

Autophagy Interplays with Apoptosis and Cell Cycle Regulation in the Growth Inhibiting Effect of Trisenox in HEP-2, a Laryngeal Squamous Cancer

  • Débora Lima PereiraAffiliated withDepartamento de Estomatologia, Hospital AC Camargo
  • , Ana Carolina dos Santos FerreiraAffiliated withPrograma de Pós-Graduação em Oncologia do Instituto Nacional de Câncer (PPGO-INCA) Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)
  • , Giselle Pinto de FariaAffiliated withDepartamento de Biorregulação, Instituto de Ciências da Saúde (ICS), Universidade Federal da Bahia (UFBA)
  • , Jolie Kiemlian KweeAffiliated withCoordenação de Pesquisa, INCA Email author 

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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.


Laryngeal squamous cancer Trisenox L-buthionine sulfoximine Autophagy Apoptosis