Vitamin E succinate induces ceramide-mediated apoptosis in head and neck squamous cell carcinoma in vitro and in vivo

Xinbin Gu, Xiaodong Song, Yongheng Dong, Hui Cai, Eric Walters, Renshu Zhang, Xiaowu Pang, Tianpei Xie, Yinhan Guo, Rajagopalan Sridhar, Joseph A. Califano

Research output: Contribution to journalArticle

Abstract

Purpose: Vitamin E succinate (α-TOS) inhibits the growth of cancer cells without unacceptable side effects. Therefore, the mechanisms associated with the anticancer action of α-TOS, including ceramide-mediated apoptosis, were investigated using head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Experimental Design: Five different human HNSCC cell lines (JHU-011, JHU-013, JHU-019, JHU-022, and JHU-029) were treated with α-TOS, and its effects on cell proliferation, cell cycle progression, ceramide-mediated apoptosis, and ceramide metabolism were evaluated. The anticancer effect of α-TOS was also examined on JHU-022 solid tumor xenograft growth in immunodeficient mice. Results: α-TOS inhibited the growth of all the HNSCC cell lines in vitro in a dose- and time-dependent manner. Thus, JHU-013 and JHU-022 cell lines were more sensitive to α-TOS than the other cell lines. Cellular levels of ceramide, sphingomyelinase activity, caspase-3, and p53 were elevated with increasing time of exposure to α-TOS. The degradation of poly(ADP-ribose) polymerase protein in JHU-022 cells treated with α-TOS provided evidence for apoptosis. The amounts of nuclear factor κB, Bcl-2, and Bcl-XL proteins were reduced in the cells treated with α-TOS for 6 hours. The levels of caspase-9, murine double minute-2, and IκB-α proteins were unchanged after α-TOS treatment. I.p. administration of α-TOS slowed tumor growth in immunodeficient mice. Conclusions: α-TOS showed promising anticancer effects to inhibit HNSCC growth and viability in vivo and in vitro. The induction of enzymes involved in ceramide metabolism by α-TOS suggests that ceramide-mediated apoptosis may expand therapeutic strategies in the treatment of carcinoma.

Original languageEnglish (US)
Pages (from-to)1840-1848
Number of pages9
JournalClinical Cancer Research
Volume14
Issue number6
DOIs
StatePublished - Mar 15 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Gu, X., Song, X., Dong, Y., Cai, H., Walters, E., Zhang, R., Pang, X., Xie, T., Guo, Y., Sridhar, R., & Califano, J. A. (2008). Vitamin E succinate induces ceramide-mediated apoptosis in head and neck squamous cell carcinoma in vitro and in vivo. Clinical Cancer Research, 14(6), 1840-1848. https://doi.org/10.1158/1078-0432.CCR-07-1811