The outcome of 5-ALA-mediated photodynamic treatment in melanoma cells is influenced by vitamin C and heme oxygenase-1
The outcome of 5-ALA-mediated photodynamic treatment in melanoma cells is influenced by vitamin C and heme oxygenase-1
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DOI：
10.1002/biof.129
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发表时间：
2011-01-01
期刊：
影响因子：
6
通讯作者：
Breusing, Nicolle
中科院分区：
文献类型：
--
作者：
Grimm, Stefanie;Mvondo, Dagmar;Breusing, Nicolle
光动力学疗法（PDT）是一种重要的临床肿瘤治疗方法。它涉及给予光敏剂，然后用光激活光敏剂并诱导细胞死亡。潜在的机制是活性氧（ROS）的产生增加，导致氧化应激，随后是细胞死亡。然而，PDT的有效性是有限的，由于启动内源性救援反应系统，如血红素加氧酶-1（HO-1）在肿瘤细胞。近年来，抗氧化剂补充剂的消费已变得普遍，但外源性应用的抗氧化剂对癌症治疗结果的影响仍不清楚。因此，本研究旨在探讨外源性抗氧化剂是否可以降低光动力治疗中ROS诱导的细胞毒性。在暴露于光动力学处理之前，将不同剂量的番茄红素、β-胡萝卜素、维生素C、N-乙酰半胱氨酸、trolox和N-叔丁基-α-苯基硝酮给予人黑素瘤细胞。补充维生素C导致细胞死亡率显著降低，而其他测试的抗氧化剂对细胞活力和氧化应激标志物没有影响。维生素C与HO-1活性抑制剂锌原卟啉IX（ZnPPIX）的同时应用引起了相当大的光动力处理诱导的细胞毒性相比，ZnPPIX单独减少。可以总结的是，外源性应用的抗氧化剂不具有对光动力处理的保护性反应的主导作用。然而，有必要进一步研究更多的抗氧化剂和其他物质，这可能会影响光动力治疗在癌症治疗中的结果。(C)2010年国际生物化学与分子生物学联合会
Photodynamic therapy (PDT) is an important clinical approach for cancer treatment. It involves the administration of a photosensitizer, followed by its activation with light and induction of cell death. The underlying mechanism is an increased production of reactive oxygen species (ROS) leading to oxidative stress, which is followed by cell death. However, effectiveness of PDT is limited due to an initiation of endogenous rescue response systems like heme oxygenase-1 (HO-1) in tumor cells. In recent years, consuming of antioxidant supplements has become widespread, but the effect of exogenously applied antioxidants on cancer therapy outcome remains unclear. Thus, this study was aimed to investigate if exogenous antioxidants might decrease ROS-induced cytotoxicity in photodynamic treatment. Lycopene, beta-carotene, vitamin C, N-acetylcysteine, trolox, and N-tert-butyl-alpha-phenylnitrone in different doses were administered to human melanoma cells prior exposure to photodynamic treatment.. Supplementation with vitamin C resulted in a significant decrease of the cell death rate, whereas the other tested antioxidants had no effect on cell viability and oxidative stress markers. The simultaneous application of vitamin C with the HO-1 activity inhibitor zinc protoporphyrine IX (ZnPPIX) caused a considerable decrease of photodynamic treatment-induced cytotoxicity compared to ZnPPIX alone. It can be summarized that exogenously applied antioxidants do not have a leading role in the protective response against photodynamic treatment. However, further studies are necessary to investigate more antioxidants and other substances, which might affect the outcome of photodynamic treatment in cancer therapy. (C) 2010 International Union of Biochemistry and Molecular Biology, Inc.