Thymosin α1 suppresses proliferation and induces apoptosis in human leukemia cell lines

Thymosin alpha(1)(T alpha(1)), 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 T alpha(1) 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 T alpha(1), 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 T alpha(1). It is noteworthy that K562 and K562/ADM were more sensitive than HL-60 cells when subjected to T alpha(1). Furthermore, HepG-2, the human hepatoma cell line, displayed significant less sensitivity to T alpha(1) than all the human leukemia cell lines. D-Tubocurarine (TUB), a nicotinic acetylcholine receptors (nAChRs) antagonist, significantly antagonized the inhibition effects induced by T alpha(1), whereas atropine, a muscaric acetylcholine receptor antagonist, did not exhibit such effects. All the results indicate that T alpha(1) was able to significantly suppress proliferation and induce apoptosis in human leukemia cell lines. (c) 2006 Elsevier Inc. All rights reserved.