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  • Open Access


    Ritonavir Interacts With Belinostat to Cause Endoplasmic Reticulum Stress and Histone Acetylation in Renal Cancer Cells

    Makoto Isono, Akinori Sato, Kazuki Okubo, Takako Asano, Tomohiko Asano

    Oncology Research, Vol.24, No.5, pp. 327-335, 2016, DOI:10.3727/096504016X14666990347635

    Abstract The histone deacetylase (HDAC) inhibitor belinostat increases the amount of unfolded proteins in cells by promoting the acetylation of heat shock protein 90 (HSP90), thereby disrupting its chaperone function. The human immunodeficiency virus protease inhibitor ritonavir, on the other hand, not only increases unfolded proteins by suppressing HSP90 but also acts as a proteasome inhibitor. We thought that belinostat and ritonavir together would induce endoplasmic reticulum (ER) stress and kill renal cancer cells effectively. The combination of belinostat and ritonavir induced drastic apoptosis and inhibited the growth of renal cancer cells synergistically. Mechanistically, the combination More >

  • Open Access


    Oxysterol-Binding Protein-Related Protein 8 Inhibits Gastric Cancer Growth Through Induction of ER Stress, Inhibition of Wnt Signaling, and Activation of Apoptosis

    Xiaohe Guo*, Lanfang Zhang*, Yingying Fan*, Dezhong Zhang, Lei Qin*, Shuping Dong*, Guangyan Li*

    Oncology Research, Vol.25, No.5, pp. 799-808, 2017, DOI:10.3727/096504016X14783691306605

    Abstract Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. Oxysterol-binding proteinrelated protein 8 (ORP8) functions as a sterol sensor that regulates a number of cellular functions. We showed that ORP8 expression was significantly lower in GC tissues and cells. Overexpression of ORP8 significantly inhibited GC cell proliferation in several GC cells. The formation of colonies in AGS cells was inhibited by the overexpression of ORP8. Moreover, overexpression of ORP8 significantly decreased implanted tumor growth in nude mice. Overexpression of ORP8 resulted in a significant increase in CHOP and GRP78 expression and the… More >

  • Open Access


    A Wnt Pathway Activator Induces Apoptosis and Cell Death in Mouse Monocytic Leukemia Cells

    Yoshiro Kato*, Yoshikazu Naiki, Takayuki Komatsu, Kazuko Takahashi, Jiro Nakamura*, Naoki Koide

    Oncology Research, Vol.25, No.4, pp. 479-483, 2017, DOI:10.3727/096504016X14721731148893

    Abstract A Wnt agonist, 2-amino-4-[3,4-(methylenedioxy)benzylamino]-6-(3-methoxyphenyl) pyrimidine, is a cellpermeable pyrimidine compound that has been shown to mimic the effect of Wnt. In this study, leukemic mouse cell lines, RAW 264.7 and J774.1, were incubated with the Wnt agonist. The Wnt agonist showed cell death in the concentration of 1–10 mM. The Wnt agonist did not show inhibition of GSK-3β activity but induced β-catenin accumulation in the nucleus. The Wnt agonist showed caspase-independent cell death, but no further involvement in cell death ER stress signaling. Here we discuss the possible mechanism of Wnt agonist-induced apoptotic cell death More >

  • Open Access


    2-Deoxy-d-glucose Suppresses the In Vivo Antitumor Efficacy of Erlotinib in Head and Neck Squamous Cell Carcinoma Cells

    Arya Sobhakumari*1, Kevin P. Orcutt†‡1, Laurie Love-Homan§, Christopher E. Kowalski†‡, Arlene D. Parsons, C. Michael Knudson†‡§¶, Andrean L. Simons*†‡§¶

    Oncology Research, Vol.24, No.1, pp. 55-64, 2016, DOI:10.3727/096504016X14586627440192

    Abstract Poor tumor response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is a significant challenge for effective treatment of head and neck squamous cell carcinoma (HNSCC). Therefore, strategies that may increase tumor response to EGFR TKIs are warranted in order to improve HNSCC patient treatment and overall survival. HNSCC tumors are highly glycolytic, and increased EGFR signaling has been found to promote glucose metabolism through various mechanisms. We have previously shown that inhibition of glycolysis with 2-deoxy-d-glucose (2DG) significantly enhanced the antitumor effects of cisplatin and radiation, which are commonly used to treat… More >

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