Herbimycin A enhances apoptotic effect of chemotherapeutic drugs on K562 cells.
OBJECTIVE
To explore the anti-apoptotic mechanism and the effective apoptosis-inducing method in chronic myelogenous leukemia (CML) cells.


METHODS
K562 cell line was used to observe the effect of combination of herbimycin A (HMA), a tyrosine kinase inhibitor, and chemotherapeutic agents on the induction of apoptosis.


RESULTS
HMA or chemotherapeutic agents could inhibit the proliferation but not significantly induce apoptosis of K562 cells. However, HMA significantly enhanced apoptosis when combined with chemotherapeutic agents. Addition of sulfhydryl compound to the cultures to conjugate HMA completely abrogated this enhancing effect on K562 cells.


CONCLUSIONS
HMA increases the sensitivity of CML cells to chemotherapeutic agents by inactivating tyrosine kinase activity. It is promising that combination of HMA with conventional chemotherapeutic drugs may be a new strategy in the treatment of CML.
Institute of Hematology, People's Hospital, Beijing Medical University, Beijing 100044, China.
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Ren
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Chen
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Lu
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones; D005047:Etoposide / Q000494:pharmacology; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D020014:K562 Cells / Q000187:drug effects*; D047029:Lactams, Macrocyclic; D008942:Mitoxantrone / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D013713:Teniposide / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D011809:Quinones; D017828:Rifabutin; D005047:Etoposide; C020754:herbimycin; D013713:Teniposide; D008942:Mitoxantrone; D011505:Protein-Tyrosine Kinases