Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents
Abstract
1. Introduction
2. Microtubules and Tubulins
3. Microtubule Targeting Agents (MTAs)
3.1. Background
3.2. Vinca Alkaloids
3.3. Taxanes
3.4. MTA Chemoresistance
4. BCL2 Family of Proteins
4.1. Anti-Apoptotic BCL2 Family and MTAs
4.2. BCL2
4.3. BCLxL
4.4. BCLW and BFL1/A1
4.5. MCL1
5. Combination of BCL2 Family Inhibitors and MTAs
6. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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MTA | Protein | Cell Type/Model | Effect | Reference |
---|---|---|---|---|
Paclitaxel | BCL2 | Breast, Lung, Prostate | * Presence sensitizes | [37,39] |
BCL2 | Leukemia | Presence induces resistance; paclitaxel decreases BCL2 mRNA expression | [74,75] | |
BCLxL | Leukemia, Colon | Upregulation induces resistance, inhibition sensitizes | [76] | |
BCLW | Leukemia | Knockdown/out sensitizes | [77] | |
BFL1/A1 | Leukemia | Upregulation induces resistance | [78] | |
Docetaxel | BCLxL | Lung, Myeloma | Inhibition sensitizes | [79] |
MCL1 | Prostate | * Inhibition or downregulation sensitizes | [80,81] | |
Vincristine | BCL2 | Leukemia | Treatment decreases BCL2 mRNA expression | [75] |
Vinblastine | MCL1 | HeLa | Treatment decreases MCL1 protein levels | [82,83] |
Vinflunine | BFL1/A1 | Lymphoma | Increase linked with resistance | [84] |
BH3 Mimetic | MCL1 | BFL1/A1 | BCLW | BCLxL | BCL2 | Cell Type/Model | Effect | Reference |
---|---|---|---|---|---|---|---|---|
ABT-737 | X | X | X | Melanoma, Breast, Prostate, Liver | Sensitizes cells to paclitaxel or docetaxel | [100,102,103] | ||
ABT-263 | X | X | X | Prostate | Additive with vincristine; synergy with paclitaxel | [104,109] | ||
ABT-199 | X | Leukemia, Lymphoma | Approved for CLL; sensitizes cells to paclitaxel | [95,110] | ||||
WEHI-539 | X | Colon | Sensitizes to Paclitaxel | [90] | ||||
Sabutoclax | X | X | X | X | X | Prostate | Sensitizes to docetaxel | [81,93] |
AT-101 | X | X | X | X | Breast | Synergizes with paclitaxel | [111,112] | |
S63845 | X | Breast | Synergizes with docetaxel | [107,108] | ||||
A1210477 | X | [79] | ||||||
AMG-176 | X | [113] | ||||||
AZD-5991 | X | [114] |
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Whitaker, R.H.; Placzek, W.J. Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents. Cells 2019, 8, 346. https://doi.org/10.3390/cells8040346
Whitaker RH, Placzek WJ. Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents. Cells. 2019; 8(4):346. https://doi.org/10.3390/cells8040346
Chicago/Turabian StyleWhitaker, Robert H., and William J. Placzek. 2019. "Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents" Cells 8, no. 4: 346. https://doi.org/10.3390/cells8040346
APA StyleWhitaker, R. H., & Placzek, W. J. (2019). Regulating the BCL2 Family to Improve Sensitivity to Microtubule Targeting Agents. Cells, 8(4), 346. https://doi.org/10.3390/cells8040346