Sangfelt O, Erickson S, Castro J, Heiden T, Einhorn S, Grandér D
Department of Oncology/Pathology, Karolinska Hospital and Institute, Stockholm, Sweden.
Cell Growth Differ. 1997 Mar;8(3):343-52.
IFNs are capable of modulating a variety of cellular responses, including cell growth and apoptosis. The prospective connections between these two biological responses are not fully understood, and the molecular mechanisms underlying the effects of IFNs on these processes are not completely defined. We have investigated the relationship between IFN-alpha-induced apoptosis and cell cycle arrest in three hematopoietic cell lines, Daudi, U-266, and H9. It was found that IFN-alpha was a rapid and potent inducer of apoptosis in H9 and U-266 cells, whereas IFN-alpha-induced cell cycle arrest in Daudi cells is not associated with the onset of apoptosis. In H9 cells, apoptosis occurs without a preceding cell cycle block, whereas in U-266 cells, apoptosis occurs subsequent to G1 arrest. Cell cycle arrest per se, induced by serum starvation or treatment with aphidicolin, had only minor effects on the viability of these cell lines and did not abrogate the apoptosis-inducing capacity of IFN-alpha. Additionally, IFN-alpha-induced apoptosis occurred in cells from all cell cycle phases. Thus, we conclude that IFN-alpha-induced apoptosis seems to occur independent of cell growth inhibition. There were no changes in Bcl-2 or Bax protein levels that could account for the apoptosis-inducing effects of IFN-alpha in these cell lines. Moreover, examination of p53 status suggests that IFN-alpha-induced apoptosis in the U-266 and H9 cell lines occurs through a p53-independent pathway.
干扰素能够调节多种细胞反应，包括细胞生长和凋亡。这两种生物学反应之间的潜在联系尚未完全明了，干扰素对这些过程产生影响的分子机制也未完全明确。我们研究了α干扰素诱导的凋亡与三种造血细胞系（Daudi、U - 266和H9）细胞周期停滞之间的关系。结果发现，α干扰素是H9和U - 266细胞中快速且有效的凋亡诱导剂，而α干扰素在Daudi细胞中诱导的细胞周期停滞与凋亡的发生无关。在H9细胞中，凋亡在没有先前细胞周期阻滞的情况下发生，而在U - 266细胞中，凋亡在G1期停滞之后发生。血清饥饿或用阿非迪霉素处理诱导的细胞周期停滞本身对这些细胞系的活力只有轻微影响，并且不会消除α干扰素的凋亡诱导能力。此外，α干扰素诱导的凋亡发生在所有细胞周期阶段的细胞中。因此，我们得出结论，α干扰素诱导的凋亡似乎独立于细胞生长抑制而发生。在这些细胞系中，Bcl - 2或Bax蛋白水平没有变化可以解释α干扰素的凋亡诱导作用。此外，对p53状态的检测表明，U - 266和H9细胞系中α干扰素诱导的凋亡是通过一条不依赖p53的途径发生的。
