Thymosin alpha1 suppresses proliferation and induces apoptosis in human leukemia cell lines.
Thymosin alpha1 (Talpha1), a 28-amino acid peptide, is a well-known immune system enhancer for the treatment of various diseases. In the present investigation, the effects of Talpha1 on the proliferation and apoptosis of human leukemia cell lines (HL-60, K562 and K562/ADM) were studied. The proliferation was significantly depressed after 96 h of treatment with Talpha1, and obvious signs of apoptosis, i.e., cell morphology, nuclei condensation and Annexin V binding, were observed thereafter. Moreover, the up-regulation of Fas/Apol (CD95) and decrease in bcl-2 anti-apoptotic gene expression were observed in apoptotic cells. The expression and the function of P-glycoprotein (P-gp) can be slightly inhibited by Talpha1. It is noteworthy that K562 and K562/ADM were more sensitive than HL-60 cells when subjected to Talpha1. Furthermore, HepG-2, the human hepatoma cell line, displayed significant less sensitivity to Talpha1 than all the human leukemia cell lines. D-Tubocurarine (TUB), a nicotinic acetylcholine receptors (nAChRs) antagonist, significantly antagonized the inhibition effects induced by Talpha1, whereas atropine, a muscarinic acetylcholine receptor antagonist, did not exhibit such effects. All the results indicate that Talpha1 was able to significantly suppress proliferation and induce apoptosis in human leukemia cell lines.
Fan
Ying-zhe
YZ
Department of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou 73000, PR China.
Chang
Hui
H
Yu
Ye
Y
Liu
Jing
J
Wang
Rui
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019254:Genes, bcl-2; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D014403:Tubocurarine / Q000378:metabolism / Q000494:pharmacology; D019014:fas Receptor / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017304:Annexin A5; D000970:Antineoplastic Agents; D011950:Receptors, Cholinergic; D019014:fas Receptor; D013947:Thymosin; D000077596:Thymalfasin; D014403:Tubocurarine