Reynolds S, Cederberg H, Chakrabarty S
Division of Pathology and Laboratory Medicine, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Clin Exp Metastasis. 2000;18(4):309-12. doi: 10.1023/a:1011071907047.
The ability of the naturally occurring ether lipid, 1-O (2 methoxy) hexadecyl glycerol (MHG), and phenylbutyrate (BP) to inhibit cellular proliferation, anchorage-independent growth and cellular invasion in the human prostate cancer LnCap and DU145 cells was determined. Both MHG and PB inhibited the malignant properties of these prostate cancer cells. The concentrations required to achieve similar inhibitory effect, however, were significantly different for these two agents. MHG inhibited cell growth with equal potency in these cell lines with an IC-50 value of 93 microM for LnCap, and 97 microM for DU145. The IC-50 values for PB were 1.3 mM and 7.3 mM, respectively, for LnCap and DU145 cells. Both MHG and PB (IC-50 concentrations) inhibited the anchorage-independent growth and cellular invasion in these cells. Over 50% inhibition of anchorage-independent growth was achieved for both LnCap and DU145 cells by PB, while a lesser degree of inhibition was achieved with MHG. Both MHG- and PB-treated cells showed a reduced propensity to invade matrigels. Invasion of PB-treated LnCap and DU145 cells was reduced, respectively, by approximate 41 and 30% when compared to untreated control cells, while invasion of MHG-treated LnCap and DU145 cells was reduced to a lesser extent. Because differentiation-inducing agents may possess chemopreventive properties, the use of naturally occurring MHG and nontoxic PB in the chemoprevention of malignant diseases warrants further investigation.
测定了天然存在的醚脂1-O(2-甲氧基)十六烷基甘油(MHG)和苯丁酸盐(BP)抑制人前列腺癌LnCap和DU145细胞的细胞增殖、非贴壁依赖性生长及细胞侵袭的能力。MHG和PB均抑制这些前列腺癌细胞的恶性特性。然而,这两种药物达到相似抑制效果所需的浓度显著不同。MHG在这些细胞系中以同等效力抑制细胞生长,对LnCap细胞的IC-50值为93微摩尔,对DU145细胞为97微摩尔。PB对LnCap和DU145细胞的IC-50值分别为1.3毫摩尔和7.3毫摩尔。MHG和PB(IC-50浓度)均抑制这些细胞的非贴壁依赖性生长及细胞侵袭。PB对LnCap和DU145细胞的非贴壁依赖性生长均实现了超过50%的抑制,而MHG的抑制程度较小。经MHG和PB处理的细胞侵袭基质胶的倾向均降低。与未处理的对照细胞相比,经PB处理的LnCap和DU145细胞的侵袭分别降低了约41%和30%,而经MHG处理的LnCap和DU145细胞的侵袭降低程度较小。由于诱导分化剂可能具有化学预防特性,天然存在的MHG和无毒的PB在恶性疾病化学预防中的应用值得进一步研究。