Abstract | BACKGROUND: MATERIALS AND METHODS: We used an inhibitor and an activator of the phosphatidylinositol-3 kinase-Akt pathway in cell survival and caspase-3 assays, an HPLC method for determining released cytochrome c and immunoblotting for detecting protein phosphorylation. RESULTS: Activation of Akt increased paclitaxel resistance by increasing Bad phosphorylation, leading to decreased release of mitochondrial cytochrome c and caspase-3-mediated apoptosis. On the other hand, inhibition of Akt prevented paclitaxel resistance by enhancing the effects of paclitaxel on Bad phosphorylation, mitochondrial cytochrome c release and caspase-3-mediated apoptosis, besides diminishing or abolishing the opposing effects of Akt activation. CONCLUSION: Akt-mediated Bad phosphorylation plays an important role in preservation of mitochondrial membrane systems leading to paclitaxel resistance in T24 cells.
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Authors | Arpad Szanto, Zita Bognar, Andras Szigeti, Aliz Szabo, Laszlo Farkas, Ferenc Gallyas Jr |
Journal | Anticancer research
(Anticancer Res)
Vol. 29
Issue 1
Pg. 159-64
(Jan 2009)
ISSN: 0250-7005 [Print] Greece |
PMID | 19331146
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- BAD protein, human
- Chromones
- Morpholines
- bcl-Associated Death Protein
- 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
- Cytochromes c
- Phosphatidylinositol 3-Kinases
- Oncogene Protein v-akt
- Caspase 3
- Paclitaxel
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Topics |
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Carcinoma, Transitional Cell
(drug therapy, enzymology, metabolism)
- Caspase 3
(metabolism)
- Chromones
(pharmacology)
- Cytochromes c
(metabolism)
- Drug Resistance, Neoplasm
- Enzyme Activation
- Humans
- Mitochondrial Membranes
(enzymology, metabolism)
- Morpholines
(pharmacology)
- Oncogene Protein v-akt
(antagonists & inhibitors, metabolism)
- Paclitaxel
(pharmacology)
- Phosphatidylinositol 3-Kinases
(metabolism)
- Phosphorylation
- Urinary Bladder Neoplasms
(drug therapy, enzymology, metabolism)
- bcl-Associated Death Protein
(metabolism)
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