Decursin and PDBu: two PKC activators distinctively acting in the megakaryocytic differentiation of K562 human erythroleukemia cells.
Protein kinase C (PKC) plays an important role in the proliferation and differentiation of various cell types including normal and leukemic hematopoietic cells. Phorbol 12,13-dibutyrate (PDBu) induces the megakaryocytic differentiation of K562 human erythroleukemia cells through PKC activation. Decursin, a pyranocoumarin from Angelica gigas, exhibits the cytotoxic effects on various human cancer cell lines and in vitro PKC activation. We report here the differences between two PKC activators, tumor-suppressing decursin and tumor-promoting PDBu, in their actions on the megakaryocytic differentiation of K562 cells. First of all, decursin inhibited PDBu-induced bleb formation in K562 cells. Decursin also inhibited the PDBu-induced megakaryocytic differentiation of K562 cells that is characterized by an increase in substrate adhesion, the secretion of granulocyte/macrophage colony stimulating factor (GM-CSF) and interleukin-6 (IL-6), and the surface expression of integrin beta3. The binding of PDBu to PKC was competitively inhibited by decursin. Decursin induced the more rapid down-regulation of PKC alpha and betaII isozymes than that induced by PDBu in K562 cells. Unlike PDBu, decursin promoted the translocation of PKC alpha and betaII to the nuclear membrane. Decursin-induced faster down-regulation and nuclear translocation of PKC alpha and betaII were not affected by the presence of PDBu. All these results indicate that decursin and phorbol ester are PKC activators distinctively acting in megakaryocytic differentiation and PKC modulation in K562 leukemia cells.
School of Life Sciences and Biotechnology, Korea University, Seongbuk-gu, Seoul 136-701, South Korea.
Hyeon Ho
HH
Kim
Kyung Seop
KS
Ahn
Hogyu
H
Han
Se Young
SY
Choung
Sang-Yun
SY
Choi
Ik-Hwan
IH
Kim
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000970:Antineoplastic Agents / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology; D002454:Cell Differentiation; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008533:Megakaryocytes / Q000473:pathology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D039681:Pyranocoumarins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001578:Benzopyrans; D002087:Butyrates; D039681:Pyranocoumarins; D015240:Phorbol 12,13-Dibutyrate; C101278:decursin; D011493:Protein Kinase C