| Title |
Lapatinib Induces Autophagy, Apoptosis and Megakaryocytic Differentiation in Chronic Myelogenous Leukemia K562 Cells
|
|---|---|
| Published in |
PLOS ONE, December 2011
|
| DOI | 10.1371/journal.pone.0029014 |
| Pubmed ID | |
| Authors |
Huey-Lan Huang, Yu-Chieh Chen, Yu-Chuen Huang, Kai-Chien Yang, Hsin yi Pan, Shou-Ping Shih, Yu-Jen Chen |
| Abstract |
Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptors (EGFR, or ErbB/Her) in solid tumors. Little is known about the effect of lapatinib on leukemia. Using human chronic myelogenous leukemia (CML) K562 cells as an experimental model, we found that lapatinib simultaneously induced morphological changes resembling apoptosis, autophagy, and megakaryocytic differentiation. Lapatinib-induced apoptosis was accompanied by a decrease in mitochondrial transmembrane potential and was attenuated by the pancaspase inhibitor z-VAD-fmk, indicating a mitochondria-mediated and caspase-dependent pathway. Lapatinib-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1. Further, autophagy inhibitor 3-methyladenine as well as autophagy-related proteins Beclin-1 (ATG6), ATG7, and ATG5 shRNA knockdown rescued the cells from lapatinib-induced growth inhibition. A moderate number of lapatinib-treated K562 cells exhibited features of megakaryocytic differentiation. In summary, lapatinib inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, and megakaryocytic differentiation in human CML K562 cells. This distinct activity of lapatinib against CML cells suggests potential for lapatinib as a therapeutic agent for treatment of CML. Further validation of lapatinib activity in vivo is warranted. |
Mendeley readers
The data shown below were compiled from readership statistics for 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Spain | 1 | 2% |
| Croatia | 1 | 2% |
| United States | 1 | 2% |
| Denmark | 1 | 2% |
| Unknown | 44 | 92% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 10 | 21% |
| Researcher | 10 | 21% |
| Student > Ph. D. Student | 7 | 15% |
| Student > Doctoral Student | 5 | 10% |
| Professor > Associate Professor | 4 | 8% |
| Other | 4 | 8% |
| Unknown | 8 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 15 | 31% |
| Medicine and Dentistry | 9 | 19% |
| Biochemistry, Genetics and Molecular Biology | 9 | 19% |
| Chemistry | 3 | 6% |
| Unspecified | 1 | 2% |
| Other | 2 | 4% |
| Unknown | 9 | 19% |