他莫昔芬治疗的绝经后乳腺癌女性在联合使用辅酶Q10、烟酸和核黄素时抗氧化状态增强。
Augmented antioxidant status in Tamoxifen treated postmenopausal women with breast cancer on co-administration with Coenzyme Q10, Niacin and Riboflavin.
作者信息
Yuvaraj Srinivasan, Premkumar Vummidi Giridhar, Vijayasarathy Kothandaraman, Gangadaran Sitthu Govindaswamy Dinakaran, Sachdanandam Panchanatham
机构信息
Department of Medical Biochemistry, Dr. ALMP-GIBMS, University of Madras, Taramani Campus, Chennai 600 113, Tamil Nadu, India.
出版信息
Cancer Chemother Pharmacol. 2008 May;61(6):933-41. doi: 10.1007/s00280-007-0547-z. Epub 2007 Aug 1.
BACKGROUND
Reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide (H(2)O(2)), hydroxyl radical have been implicated in pathogenesis of various diseases including cancer and metastasis. Tamoxifen (TAM) is a non-steroidal anti-estrogen drug most widely used as an adjuvant hormonal therapy in breast cancer. TAM also has estrogenic activity on liver and endometrium causing severe oxidative stress and hypertriglycerdemia. Coenzyme Q(10) (CoQ(10)), Niacin and Riboflavin are well-known potent antioxidants and protective agents against many diseases including cancer. In this context, this study was undertaken to find if co-administration of CoQ(10), Niacin and Riboflavin along with TAM could augment the antioxidant (AO) status in postmenopausal women with breast cancer.
METHODS
The vitamin supplementation with Tamoxifen was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Plasma lipids, lipid peroxides and various circulating enzymatic and non-enzymatic antioxidants were estimated in 78 untreated, sole TAM treated and combinatorial treated group along with 46 age- and sex-matched controls.
RESULTS
Enhanced oxidative stress as evidenced by increased lipids and lipid peroxides with decreased AO levels in untreated breast cancer patients was observed. Adjuvant TAM-treated group had a limited impact on the increased oxidative stress with decreased AO status. Severe hypertriglycerdemia was observed in TAM-treated group when compared to untreated and control subjects. Combinatorial therapy (CT) of CoQ(10), Niacin and Riboflavin along with TAM decreased the oxidative stress and increased the AO status.
CONCLUSION
The antioxidant defense system is compromised in breast cancer patients. There is a shift in the oxidant / antioxidant balance in favor of lipid peroxidation (LPO), which could lead to tumour promotion observed in the disease. CT of CoQ(10), Niacin and Riboflavin along with TAM significantly increased the AO status, while decreasing lipid and lipid peroxides. The results suggest the necessity of therapeutic co-administration of antioxidants along with conventional drug to such patients. However, due to limited number of cases included in this study, more studies may be required to substantiate the results and arrive at a definitive conclusion, in terms of safety and efficacy of adding an AO therapy in treatment of breast cancer.
背景
活性氧(ROS)如超氧阴离子、过氧化氢(H₂O₂)、羟基自由基与包括癌症和转移在内的各种疾病的发病机制有关。他莫昔芬(TAM)是一种非甾体类抗雌激素药物,在乳腺癌辅助激素治疗中应用最为广泛。TAM对肝脏和子宫内膜也具有雌激素活性,会导致严重的氧化应激和高甘油三酯血症。辅酶Q₁₀(CoQ₁₀)、烟酸和核黄素是众所周知的强效抗氧化剂,对包括癌症在内的许多疾病具有保护作用。在此背景下,本研究旨在探讨CoQ₁₀、烟酸和核黄素与TAM联合使用是否能增强绝经后乳腺癌患者的抗氧化(AO)状态。
方法
给予他莫昔芬维生素补充剂90天。在治疗过程中的基线、第45天和第90天采集血样。对78例未治疗、单纯TAM治疗和联合治疗组以及46例年龄和性别匹配的对照组进行血浆脂质、脂质过氧化物以及各种循环酶和非酶抗氧化剂的评估。
结果
观察到未治疗的乳腺癌患者脂质和脂质过氧化物增加,AO水平降低,表明氧化应激增强。辅助TAM治疗组对氧化应激增加和AO状态降低的影响有限。与未治疗和对照组相比,TAM治疗组观察到严重的高甘油三酯血症。CoQ₁₀、烟酸和核黄素与TAM的联合治疗(CT)降低了氧化应激并提高了AO状态。
结论
乳腺癌患者的抗氧化防御系统受损。氧化/抗氧化平衡向有利于脂质过氧化(LPO)的方向转变,这可能导致在该疾病中观察到的肿瘤促进作用。CoQ₁₀、烟酸和核黄素与TAM的联合治疗显著提高了AO状态,同时降低了脂质和脂质过氧化物。结果表明,对此类患者在使用传统药物治疗时联合使用抗氧化剂进行治疗的必要性。然而,由于本研究纳入的病例数量有限,可能需要更多研究来证实结果,并就添加AO疗法治疗乳腺癌的安全性和有效性得出明确结论。