Selenium-enriched Arthrospira platensis potentiates docetaxel, oxaliplatin, and topotecan anticancer activity in epithelial tumors

Selenium-enriched Arthrospira platensis potentiates docetaxel, oxaliplatin, and topotecan anticancer activity in epithelial tumors
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DOI:
10.1007/s10811-016-0886-4
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发表时间:
2016-06
影响因子:
3.3
通讯作者:
C. Riva;H. Oréal
C. Riva;H. Oréal
中科院分区:
生物学3区
文献类型:
--
作者:
C. Riva;H. Oréal

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多西他赛(DOC)、奥沙利铂(OXA)和拓扑替康(TOPO)是治疗人类癌症的有效化疗药物,但它们的临床应用受到严重副作用的限制。钝顶节旋藻(Arthrospira platensis)是一种被广泛用作营养补充剂的蓝藻,它能以剂量和时间依赖的方式积累大量的硒(Se),硒是一种具有潜在抗癌作用的微量元素。本研究(1)测定了A.(2)评价了含硒的血小板单用或与DOC、OXA或TOPO联合(IC_(50)浓度)对人上皮性结直肠腺癌(Caco-2)和前列腺癌(DU 145)细胞系细胞增殖、原位凋亡和活性氧(ROS)产生的影响;(3)评价了含硒的血小板对肾癌细胞(RCC 786-0)移植小鼠肿瘤生长的体内影响。既不富硒,也不富硒。血小板的存活率显著降低。用Se + DOC、Se + OXA或Se + TOPO富集的A孵育Caco-2或DU 145细胞。Platensis通过促进caspase-3介导的细胞凋亡和减少ROS的产生,使每种药物的细胞毒性显著增加85- 99%(与单独用抗癌药物处理的细胞相比)。在体内,用Se + TOPO富集的A.与安慰剂或富硒A相比,4周的血小板减少显著降低肿瘤生长。Platensisalone(P< 0.05)。富硒抗有丝分裂药物A.使用富硒A. Platensisas作为抗癌药物递送的载体可以代表开发有效且毒性较小的抗癌治疗的新策略。
Docetaxel (DOC), oxaliplatin (OXA), and topotecan (TOPO) are effective chemotherapy agents in human cancers, but their clinical use is limited by severe side effects.Arthrospira platensis, a cyanobacterium that is widely used as a nutritional supplement, can accumulate in a dose- and time-dependent manner high amounts of selenium (Se), a trace element with potential anticancer effects. In this study, we (1) tested the in vitro effects ofA. platensisenriched with Se alone or combined with DOC, OXA, or TOPO (IC50concentrations) on cell proliferation, in situ apoptosis, and reactive oxygen species (ROS) production in human epithelial colorectal adenocarcinoma (Caco-2) and prostate cancer (DU145) cell lines and (2) assessed the in vivo effect on tumor growth in mice xenografted with renal carcinoma cells (RCC 786-0). Neither Se nor Se-enrichedA. platensisaffected the viability significantly. Incubation of Caco-2 or DU145 cells with Se + DOC, Se + OXA, or Se + TOPO-enrichedA. platensisincreased significantly the cytotoxicity of each drug by 85–99 % (compared with cells treated with anticancer drug alone) through promotion of caspase-3-mediated apoptosis and reduction of ROS production. In vivo, treatment with Se + TOPO-enrichedA. platensisfor 4 weeks significantly reduced tumor growth compared with placebo or Se-enrichedA. platensisalone (p< 0.05). The Se + antimitotic drug-enrichedA. platensisformulation using Se-enrichedA. platensisas a vector for anticancer drug delivery could represent a new strategy for the development of effective and less toxic treatments against cancer.