Gottfried, Eva and Rogenhofer, Sebastian and Waibel, Heidi and Kunz-Schughart, Leoni A. and Reichle, Albrecht and Wehrstein, Monika and Peuker, Alice and Peter, Katrin and Hartmannsgruber, Gabi and Andreesen, Reinhard and Kreutz, Marina (2011) Pioglitazone modulates tumor cell metabolism and proliferation in multicellular tumor spheroids. CANCER CHEMOTHERAPY AND PHARMACOLOGY, 67 (1). pp. 117-126. ISSN 0344-5704, 1432-0843
Full text not available from this repository. (Request a copy)Abstract
The anti-diabetic thiazolidinedione compound pioglitazone, a peroxisome proliferator-activated receptor-gamma agonist, and selective cyclooxygenase-2 inhibitors are clinically used in patients with advanced malignancies. Several previously published in vivo and in vitro studies showed growth inhibitory effects on different cancer cell lines. However, the underlying mechanisms are fairly unclear. Here, we analyzed the effects of pioglitazone in combination with other drugs in a three-dimensional multicellular tumor spheroid culture system (MCTS) generated from the two prostate carcinoma cell lines PC3 and LNCaP. As expected, pioglitazone also inhibited tumor cell proliferation in the MCTS system. Further studies revealed that pioglitazone lowered the pH of the culture medium, decreased oxygen consumption and increased lactate secretion in both tumor cell lines. Other glitazones, troglitazone and ciglitazone, had similar effects. The combination of pioglitazone with 2-deoxyglucose, a potent inhibitor of glycolysis, had an additive effect on the inhibition of cell proliferation and led to MCTS disintegration. Our data propose a new mechanism of growth inhibition by pioglitazone through modulation of the tumor cell metabolism.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED-RECEPTOR-GAMMA; HUMAN PROSTATE-CANCER; PPAR-GAMMA; IN-VITRO; CARCINOMA CELLS; APOPTOSIS; THIAZOLIDINEDIONES; AGONISTS; ROSIGLITAZONE; EXPRESSION; Pioglitazone; Glitazones; Lactate; pH; Tumor cell proliferation; 2-Deoxyglucose |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jun 2020 08:57 |
| Last Modified: | 29 Jun 2020 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21501 |
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