Anti-tumor effect of ascorbic acid, lysine, proline, arginine, and epigallocatechin gallate on prostate cancer cell lines PC-3, LNCaP, and DU145.

M Waheed Roomi, Vadim Ivanov, Tatiana Kalinovsky, Aleksandra Niedzwiecki, Matthias Rath
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Abstract

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.

抗坏血酸、赖氨酸、脯氨酸、精氨酸和表没食子儿茶素没食子酸酯对前列腺癌细胞PC-3、LNCaP和DU145的抗肿瘤作用
一旦前列腺癌发生转移,目前的治疗方法通常是无效的。由于特定营养素具有抗肿瘤特性,我们研究了一种独特配方(NS)的赖氨酸、脯氨酸、精氨酸、抗坏血酸和表没食子儿茶素没食子酸酯对人类前列腺癌细胞系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、MMP表达和侵袭潜力。细胞系DU145、PC-3和LNCaP与不同浓度的NS近融合处理。24 h后用MTT法检测细胞增殖,用明胶酶酶谱法检测条件培养基中MMP的表达,用Matrigel法检测细胞侵袭活性。当浓度为50 μ g/ml时,对PC-3细胞增殖无明显抑制作用,但当浓度为500 μ g/ml时,对PC-3细胞有明显的抑制作用。用NS处理LNCaP细胞时,100 μ g/ml对LNCaP细胞增殖的抑制作用为对照的80%。NS对DU145细胞增殖的抑制作用呈剂量依赖性,在1000 μ g/ml浓度下可降低47%。NS对PC-3细胞的MMP-2和MMP-9表达和pma处理(200 ng/ml) DU145细胞的MMP-9表达均有剂量依赖性抑制作用。LNCaP细胞培养中均未检测到MMP-2和MMP-9溶胶活性。500 μ g/ml和1000 μ g/ml分别完全抑制Matrigel对DU145和LNCaP细胞的侵袭。抑制MMP的表达和侵袭表明,所研究的营养混合物是治疗前列腺癌的一种有效的天然抗癌剂。
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