The anticancer drug imatinib induces cellular autophagy.
The tyrosine kinase inhibitor imatinib (Gleevec, Novartis Pharmaceuticals Corporation; Basel, Switzerland) is a powerful drug for treatment of chronic myelogenous leukemia (CML) and other malignancies. It selectively targets various tyrosine kinases, thereby leading to growth arrest of respective cancer cells. Given its wide application, it is of high importance to know all related underlying molecular mechanisms. We had previously found that imatinib increases the cellular clearance of intracellular protein aggregates by targeting the abl pathway and thereby upregulating lysosomal activity. Here, we describe that imatinib dose dependently activates the cellular autophagy machinery in mammalian cells, independently of tissue type, species origin or immortalization status of cells. Autophagy is an archetypical cellular degradation mechanism implicated in many physiological and pathophysiological conditions. Our data link for the first time the process of autophagy with the mode of action of imatinib. Induction of autophagy might represent an additional mechanism of imatinib to induce growth arrest, promote apoptosis in cancer cells and eventually even promote tumour regression.
Ertmer
A
A
Institute of Virology, Technical University of Munich, Munich, Germany.
Huber
V
V
Gilch
S
S
Yoshimori
T
T
Erfle
V
V
Duyster
J
J
Elsässer
H-P
HP
Schätzl
H M
HM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D001549:Benzamides; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D000068877:Imatinib Mesylate; D008247:Lysosomes / Q000187:drug effects; D051379:Mice; D010588:Phagosomes / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000494:pharmacology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor; D016315:Proto-Oncogene Proteins c-abl