Roomi M Waheed, Ivanov Vadim, Kalinovsky Tatiana, Niedzwiecki Aleksandra, Rath Matthias
Matthias Rath Research, Cancer Division, 1260 Memorex Drive, Santa Clara, CA 95050, USA.
Res Commun Mol Pathol Pharmacol. 2004;115-116:251-64.
Once prostate cancer has metastasized, current treatment methods are generally ineffective. Due to the reported anti-tumor properties of specific nutrients, we investigated the effect of a unique formulation (NS) of lysine, proline, arginine, ascorbic acid, and epigallocatechin gallate on human prostate cancer cell lines: PC-3, DU145 (androgen insensitive) and LNCaP (androgen sensitive), by measuring cell proliferation, MMP expression, and invasion potential. Cell lines DU145, PC-3, and LNCaP were treated at near confluence with NS at various concentrations. Cell proliferation was measured by MTT assay after 24 hours, MMP expression was measured by gelatinase zymography in condition media, and invasion activity was measured by Matrigel. The nutrient mixture did not significantly inhibit PC-3 cell proliferation at 50 microg/ml, but showed significant antiproliferative effect at 500 ug/ml. When treated with NS, proliferation of LNCaP cells was inhibited by 80% of control at 100 microg/ml. NS showed dose-dependent inhibition of DU145 cell proliferation with 47% reduction at 1000 microg/ml. NS showed a dose-dependent inhibition of both MMP-2 and MMP-9 expression by PC-3 cells and MMP-9 expression by PMA-treated (200 ng/ml) DU145 cells. Neither MMP-2 nor MMP-9 gelatinolytic activity was detected in LNCaP cell culture. Invasion of DU145 and LNCaP cells through Matrigel was completely inhibited at 500 microg/ml and PC-3 at 1000 microg/ml. Inhibition of MMP expression and invasion suggests the mixture of nutrients studied is a potent, natural anticancer agent for the treatment of prostate cancer.
一旦前列腺癌发生转移,目前的治疗方法通常无效。鉴于特定营养素具有抗肿瘤特性的报道,我们研究了赖氨酸、脯氨酸、精氨酸、抗坏血酸和表没食子儿茶素没食子酸酯的独特配方(NS)对人前列腺癌细胞系PC-3、DU145(雄激素不敏感)和LNCaP(雄激素敏感)的影响,通过测量细胞增殖、基质金属蛋白酶(MMP)表达和侵袭潜能。用不同浓度的NS处理接近汇合状态的DU145、PC-3和LNCaP细胞系。24小时后通过MTT法测量细胞增殖,通过明胶酶谱法在条件培养基中测量MMP表达,通过基质胶测量侵袭活性。该营养混合物在50微克/毫升时对PC-3细胞增殖没有显著抑制作用,但在500微克/毫升时显示出显著的抗增殖作用。用NS处理时,LNCaP细胞在100微克/毫升时增殖受到抑制,为对照的80%。NS对DU145细胞增殖显示出剂量依赖性抑制,在1000微克/毫升时减少47%。NS对PC-3细胞的MMP-2和MMP-9表达以及经佛波酯(200纳克/毫升)处理的DU145细胞的MMP-9表达均显示出剂量依赖性抑制。在LNCaP细胞培养物中未检测到MMP-2和MMP-9的明胶酶活性。DU145和LNCaP细胞通过基质胶的侵袭在500微克/毫升时被完全抑制,PC-3细胞在1000微克/毫升时被完全抑制。MMP表达和侵袭的抑制表明所研究的营养混合物是一种用于治疗前列腺癌的有效天然抗癌剂。