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Bcl2/bcl-xl inhibitor engenders apoptosis and increases chemo-sensitivity in mesothelioma
| Content Provider | Scilit |
|---|---|
| Author | Cao, Xiaobo Rodarte, Charles Zhang, Lidong Morgan, Clinton D. Littlejohn, James Smythe, W. Roy |
| Copyright Year | 2007 |
| Description | Journal: Cancer Biology & Therapy Mesothelioma is a neoplasm of the pleura that is currently incurable by conventional therapies. Previously, we demonstrated that mesothelioma overexpresses BCL-X(L), an anti-apoptotic member of the BCL-2 family. In addition, we have shown that down regulation of BCL-X(L) using a BCL-X(L) antisense oligonucleotide engenders mesothelioma apoptotic cell death in vitro and in vivo. The purpose of this study is to evaluate the efficacy of bcl2/bcl-x(L) inhibitor, 2-methoxy antimycin A3, in inducing apoptosis and increasing chemo-sensitivity in vitro and in vivo. Several bcl-x(L) high-expression tumor cell lines and one normal human cell line were exposed to 2-methoxy antimycin A3. 2-methoxy antimycin A3 demonstrated significant growth inhibition only in these tumor cell lines, with little effect on normal human cells. Treatment with 2-methoxy antimycin A3 alone resulted in a dramatic increase in the induction of apoptosis in the cancer cells. Apoptosis occurs through decreasing mitochondrial membrane potential and caspase activation. Notably, treatment with 2-methoxy antimycin A3 does not alter BCL-2 family protein expression. Synergistic inhibition of tumor growth by the coadministration of cisplatin and 2-methoxy antimycin A3 was observed in both in vitro and in vivo experiments. Together, these findings indicate that exposure of cancer cells to small molecule Bcl-2/x(L) inhibitors such as 2-methoxy antimycin A3 alone, or in the combination with other chemotherapeutics, may represent a novel therapeutic strategy in treatment of cancer, especially mesothelioma. |
| Related Links | http://www.tandfonline.com/doi/pdf/10.4161/cbt.6.2.3626?needAccess=true https://www.landesbioscience.com/journals/cbt/cao6-2.pdf |
| Ending Page | 252 |
| Page Count | 7 |
| Starting Page | 246 |
| ISSN | 15384047 |
| e-ISSN | 15558576 |
| DOI | 10.4161/cbt.6.2.3626 |
| Journal | Cancer Biology & Therapy |
| Issue Number | 2 |
| Volume Number | 6 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2007-02-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Cancer Biology & Therapy Mesothelioma Chemo Sensitivity Xl Inhibitor Engenders |
| Content Type | Text |
| Subject | Cancer Research Pharmacology Molecular Medicine Oncology |
