Roomi M W, Bhanap B A, Roomi N W, Rath M, Niedzwiecki A
Exp Oncol. 2009 Sep;31(3):149-55.
Non-Hodgkin lymphomas incidence has increased more than 70% in last 25 years. Aggressiveness, higher relapse rate, and treatment complications pose significant barriers. Decreased food intake and side effects of treatments make cancer patients vulnerable to deficiency of essential nutrients such as vitamin C, lysine, and proline leading to the formation of weak extra cellular matrix susceptible to easy breakdown by matrix metalloproteinase enzymes. Inhibition of these enzymes has shown promise in stopping metastasis.
In this study, we investigated the effects of a specific nutrient mixture, containing ascorbic acid, lysine, proline, green tea extract among others, in most aggressive forms of non-Hodgkin's lymphoma - Burkitt's lymphoma, and T-cell lymphoma - using Raji and Jurkat cells respectively.
Nutrient mixture (NM) doses of 0, 10, 50, 100, 500, 1000 microg/ml, were used to study effects on cell proliferation, expression of matrix metalloproteinase, Matrigel invasion and apoptosis.
The results demonstrated that the dose response toxicity of the nutrient mixture on Raji cells gradually increased with increasing concentration. The nutrient mixture was non-toxic to Jurkat cells, however exhibited anti-proliferative properties at higher concentrations. Zymography demonstrated, NM had a significant inhibitory effect on matrix metalloproteinase-9 expression with total inhibition at 1000 microg/ml for Raji cells and at 500 microg/ml for Jurkat cells. The NM at 100 microg/ml completely inhibited Matrigel invasion for Raji cells, and at 1000 microg/ml for Jurkat cells. After the NM challenge virtually all Raji and Jurkat cells exposed to 1000 microg/ml were in late apoptosis.
Considering the lack of treatment options and continually increasing incidence, NM could be further explored for its therapeutic potential in Burkitt's lymphoma and T-cell lymphoma.
在过去25年中，非霍奇金淋巴瘤的发病率增加了70%以上。侵袭性、较高的复发率和治疗并发症构成了重大障碍。食物摄入量减少和治疗副作用使癌症患者易缺乏维生素C、赖氨酸和脯氨酸等必需营养素，导致形成脆弱的细胞外基质，易被基质金属蛋白酶酶分解。抑制这些酶在阻止转移方面显示出前景。
在本研究中，我们分别使用Raji细胞和Jurkat细胞，研究了一种特定营养混合物（含有抗坏血酸、赖氨酸、脯氨酸、绿茶提取物等）对最具侵袭性的非霍奇金淋巴瘤——伯基特淋巴瘤和T细胞淋巴瘤的影响。
使用0、10、50、100、500、1000微克/毫升的营养混合物（NM）剂量来研究对细胞增殖、基质金属蛋白酶表达、基质胶侵袭和细胞凋亡的影响。
结果表明，营养混合物对Raji细胞的剂量反应毒性随浓度增加而逐渐增加。营养混合物对Jurkat细胞无毒，但在较高浓度下表现出抗增殖特性。酶谱分析表明，NM对基质金属蛋白酶-9的表达有显著抑制作用，对Raji细胞在1000微克/毫升时完全抑制，对Jurkat细胞在500微克/毫升时完全抑制。100微克/毫升的NM对Raji细胞的基质胶侵袭有完全抑制作用，对Jurkat细胞在1000微克/毫升时有完全抑制作用。在NM刺激后，几乎所有暴露于1000微克/毫升的Raji和Jurkat细胞都处于晚期凋亡。
考虑到缺乏治疗选择且发病率持续上升，营养混合物在伯基特淋巴瘤和T细胞淋巴瘤中的治疗潜力值得进一步探索。
