Wang Haizhen, Liu Yongding, Gao Xueliang, Carter Christie L, Liu Zhi-Ren
Department of Biology, Georgia Cancer Center, Georgia State University, University Plaza, Atlanta, GA 30303, USA.
Cancer Lett. 2007 Mar 8;247(1):150-8. doi: 10.1016/j.canlet.2006.04.002. Epub 2006 Jun 5.
C-Phycocyanin (C-PC) from blue-green algae has been reported to have various pharmacological characteristics, including anti-inflammatory and anti-tumor activities. In this study, we expressed the beta-subunit of C-PC (ref to as C-PC/beta) in Escherichia coli. We found that the recombinant C-PC/beta has anti-cancer properties. Under the treatment of 5 microM of the recombinant C-PC/beta, four different cancer cell lines accrued high proliferation inhibition and apoptotic induction. Substantially, a lower response occurred in non-cancer cells. We investigated the mechanism by which C-PC/beta inhibits cancer cell proliferation and induces apoptosis. We found that the C-PC/beta interacts with membrane-associated beta-tubulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Under the treatment of the C-PC/beta, depolymerization of microtubules and actin-filaments were observed. The cells underwent apoptosis with an increase in caspase-3, and caspase-8 activities. The cell cycle was arrested at the G0/G1 phase under the treatment of C-PC/beta. In addition, the nuclear level of GAPDH decreased significantly. Decrease in the nuclear level of GAPDH prevents the cell cycle from entering into the S phase. Inhibition of cancer cell proliferation and induction of apoptosis may potentate the C-PC/beta as a promising cancer prevention or therapy agent.
据报道,蓝藻中的C-藻蓝蛋白(C-PC)具有多种药理特性,包括抗炎和抗肿瘤活性。在本研究中,我们在大肠杆菌中表达了C-PC的β亚基(称为C-PC/β)。我们发现重组C-PC/β具有抗癌特性。在5微摩尔重组C-PC/β的处理下,四种不同的癌细胞系出现了高增殖抑制和凋亡诱导。实质上,非癌细胞的反应较低。我们研究了C-PC/β抑制癌细胞增殖并诱导凋亡的机制。我们发现C-PC/β与膜相关的β-微管蛋白和甘油醛-3-磷酸脱氢酶(GAPDH)相互作用。在C-PC/β处理下,观察到微管和肌动蛋白丝的解聚。细胞随着半胱天冬酶-3和半胱天冬酶-8活性的增加而发生凋亡。在C-PC/β处理下,细胞周期停滞在G0/G1期。此外,GAPDH的核水平显著降低。GAPDH核水平的降低阻止细胞周期进入S期。抑制癌细胞增殖和诱导凋亡可能使C-PC/β成为一种有前景的癌症预防或治疗药物。