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Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors.
Int J Oncol. 2007 Nov; 31(5):1141-7.IJ

Abstract

The purpose of this study was to determine whether phosphatidylinositol 3-kinase (PI 3-K) inhibitors could modulate the apoptotic activity of the anticancer drugs cisplatin, 5-fluorouracil or docetaxel in an oral squamous cell carcinoma (OSCC) cell line, HSC-2. In preliminary experiments, cisplatin, 5-fluorouracil and docetaxel inhibited the proliferation of OSCC cells in a dose-dependent manner. We found that two PI 3-K inhibitors, wortmannin and LY294002, markedly suppressed the phosphorylation of Akt in OSCC cells. Treatment of OSCC cells with PI 3-K inhibitors significantly enhanced cisplatin-, 5-fluorouracil- or docetaxel-induced apoptosis. Caspase-3 and -9 inhibitors, but not a caspase-8 inhibitor, reduced anticancer drug-mediated apoptosis in PI 3-K inhibitor-treated OSCC cells, suggesting that the apoptotic pathway induced by the combination of anticancer drug therapy and PI 3-K inhibition may be functionally related to the intrinsic apoptotic pathway in OSCC cells. Expression of Bcl-2, cellular inhibitor of apoptosis protein-1 (cIAP-1), and X-linked IAP was down-regulated, and expression of Bax was up-regulated by PI 3-K inhibitors, while that of Bcl-xL, Bak and cIAP-2 was not attenuated. We also found that Bad phosphorylation was down-regulated by PI 3-K inhibitors. These results suggested that inhibition of PI 3-K enhances the susceptibility of OSCC cells to anticancer drug-mediated apoptosis through regulation of expression and post-translational modification of both pro- and anti-apoptotic proteins. These findings could potentially lead to new strategies for improving the efficacy of anticancer drugs in OSCC cells.

Authors+Show Affiliations

Department of Oral and Maxillofacial Surgery, Showa University School of Dentistry, Ota-ku, Tokyo 145-8515, Japan. iwase@senzoku.showa-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17912441

Citation

Iwase, Masayasu, et al. "Enhanced Susceptibility to Apoptosis of Oral Squamous Cell Carcinoma Cells Subjected to Combined Treatment With Anticancer Drugs and Phosphatidylinositol 3-kinase Inhibitors." International Journal of Oncology, vol. 31, no. 5, 2007, pp. 1141-7.
Iwase M, Yoshiba S, Uchid M, et al. Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors. Int J Oncol. 2007;31(5):1141-7.
Iwase, M., Yoshiba, S., Uchid, M., Takaoka, S., Kurihara, Y., Ito, D., Hatori, M., & Shintani, S. (2007). Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors. International Journal of Oncology, 31(5), 1141-7.
Iwase M, et al. Enhanced Susceptibility to Apoptosis of Oral Squamous Cell Carcinoma Cells Subjected to Combined Treatment With Anticancer Drugs and Phosphatidylinositol 3-kinase Inhibitors. Int J Oncol. 2007;31(5):1141-7. PubMed PMID: 17912441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhanced susceptibility to apoptosis of oral squamous cell carcinoma cells subjected to combined treatment with anticancer drugs and phosphatidylinositol 3-kinase inhibitors. AU - Iwase,Masayasu, AU - Yoshiba,Sayaka, AU - Uchid,Makiko, AU - Takaoka,Sayaka, AU - Kurihara,Yuji, AU - Ito,Daisuke, AU - Hatori,Masashi, AU - Shintani,Satoru, PY - 2007/10/4/pubmed PY - 2007/12/21/medline PY - 2007/10/4/entrez SP - 1141 EP - 7 JF - International journal of oncology JO - Int J Oncol VL - 31 IS - 5 N2 - The purpose of this study was to determine whether phosphatidylinositol 3-kinase (PI 3-K) inhibitors could modulate the apoptotic activity of the anticancer drugs cisplatin, 5-fluorouracil or docetaxel in an oral squamous cell carcinoma (OSCC) cell line, HSC-2. In preliminary experiments, cisplatin, 5-fluorouracil and docetaxel inhibited the proliferation of OSCC cells in a dose-dependent manner. We found that two PI 3-K inhibitors, wortmannin and LY294002, markedly suppressed the phosphorylation of Akt in OSCC cells. Treatment of OSCC cells with PI 3-K inhibitors significantly enhanced cisplatin-, 5-fluorouracil- or docetaxel-induced apoptosis. Caspase-3 and -9 inhibitors, but not a caspase-8 inhibitor, reduced anticancer drug-mediated apoptosis in PI 3-K inhibitor-treated OSCC cells, suggesting that the apoptotic pathway induced by the combination of anticancer drug therapy and PI 3-K inhibition may be functionally related to the intrinsic apoptotic pathway in OSCC cells. Expression of Bcl-2, cellular inhibitor of apoptosis protein-1 (cIAP-1), and X-linked IAP was down-regulated, and expression of Bax was up-regulated by PI 3-K inhibitors, while that of Bcl-xL, Bak and cIAP-2 was not attenuated. We also found that Bad phosphorylation was down-regulated by PI 3-K inhibitors. These results suggested that inhibition of PI 3-K enhances the susceptibility of OSCC cells to anticancer drug-mediated apoptosis through regulation of expression and post-translational modification of both pro- and anti-apoptotic proteins. These findings could potentially lead to new strategies for improving the efficacy of anticancer drugs in OSCC cells. SN - 1019-6439 UR - https://www.unboundmedicine.com/medline/citation/17912441/Enhanced_susceptibility_to_apoptosis_of_oral_squamous_cell_carcinoma_cells_subjected_to_combined_treatment_with_anticancer_drugs_and_phosphatidylinositol_3_kinase_inhibitors_ L2 - http://www.spandidos-publications.com/ijo/31/5/1141 DB - PRIME DP - Unbound Medicine ER -