Phloretin-induced apoptosis in B16 melanoma 4A5 cells and HL60 human leukemia cells.
The dihydrochalcone phloretin induced apoptosis in B16 mouse melanoma 4A5 cells and HL60 human leukemia cells. Phloretin was suggested to induce apoptosis in B16 cells mainly through the inhibition of glucose transmembrane transport. The phloretin-induced apoptosis in B16 cells was inhibited by actinomycin D, Ac-YVAD-CHO caspase-1-like inhibitor, and Ac-DEVD-CHO caspase-3-like inhibitor. During the induction of apoptosis by phloretin, the expression of Bax protein in B16 cells increased and the levels of p53, Bcl-2, and Bcl-XL proteins did not change. Our results suggested that phloretin induced apoptosis through the promotion of Bax protein expression and caspases activation. On the other hand, phloretin may induce apoptosis in HL60 cells through the inhibition of protein kinase C activity because phloretin inhibited protein kinase C activity in HL60 cells more than that in B16 cells. The phloretin induced-apoptosis in HL60 cells was not inhibited by actinomycin D and the caspase-1-like inhibitor, but slightly inhibited by the caspase-3-like inhibitor. Phloretin reduced the level of caspase 3 protein in HL60 cells, but not the level of the Bcl-2 protein. Phloretin did not increase the level of Bax protein. Phloretin was suggested to induce apoptosis in HL60 cells through the inhibition of protein kinase C activity, followed by the pathway, which is different from that in B16 cells.
Kobori
M
M
National Food Research Institute, Ministry of Agriculture, Forestry and Fisheries, Ibaraki, Japan. kobori@nfri.affrc.go.jp
Iwashita
K
K
Shinmoto
H
H
Tsushida
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016466:CHO Cells; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D006224:Cricetinae; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D010693:Phloretin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D011500:Protein Synthesis Inhibitors; D011493:Protein Kinase C; D010693:Phloretin