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姜黄素,来自印度藏红花的金色香料,是肿瘤的化学增敏剂和放射增敏剂,也是正常器官的化学保护剂和放射保护剂。

Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs.

机构信息

Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas, USA.

出版信息

Nutr Cancer. 2010;62(7):919-30. doi: 10.1080/01635581.2010.509835.

Abstract

Curcumin (diferuloylmethane), the yellow pigment in Indian saffron (Curcuma longa; also called turmeric, haldi, or haridara in the East and curry powder in the West), has been consumed by people for centuries as a dietary component and for a variety of proinflammatory ailments. Extensive research within the last decade in cell culture and in rodents has revealed that curcumin can sensitize tumors to different chemotherapeutic agents including doxorubicin, 5-FU, paclitaxel, vincristine, melphalan, butyrate, cisplatin, celecoxib, vinorelbine, gemcitabine, oxaliplatin, etoposide, sulfinosine, thalidomide, and bortezomib. Chemosensitization has been observed in cancers of the breast, colon, pancreas, gastric, liver, blood, lung, prostate, bladder, cervix, ovary, head and neck, and brain and in multiple myeloma, leukemia, and lymphoma. Similar studies have also revealed that this agent can sensitize a variety of tumors to gamma radiation including glioma, neuroblastoma, cervical carcinoma, epidermal carcinoma, prostate cancer, and colon cancer. How curcumin acts as a chemosensitizer and radiosensitizer has also been studied extensively. For example, it downregulates various growth regulatory pathways and specific genetic targets including genes for NF-κB, STAT3, COX2, Akt, antiapoptotic proteins, growth factor receptors, and multidrug-resistance proteins. Although it acts as a chemosensitizer and radiosensitizer for tumors in some cases, curcumin has also been shown to protect normal organs such as liver, kidney, oral mucosa, and heart from chemotherapy and radiotherapy-induced toxicity. The protective effects of curcumin appear to be mediated through its ability to induce the activation of NRF2 and induce the expression of antioxidant enzymes (e.g., hemeoxygenase-1, glutathione peroxidase, modulatory subunit of gamma-glutamyl-cysteine ligase, and NAD(P)H:quinone oxidoreductase 1, increase glutathione (a product of the modulatory subunit of gamma-glutamyl-cysteine ligase), directly quench free radicals, and inhibit p300 HAT activity. These preclinical studies are expected to lead to clinical trials to prove the potential of this age-old golden spice for treating cancer patients.

摘要

姜黄素(双阿魏酰甲烷)是印度藏红花(姜黄;在东方也被称为 turmeric、haldi 或 haridara,在西方则被称为咖喱粉)中的黄色色素,几个世纪以来,人们一直将其作为膳食成分,并用于治疗各种炎症性疾病。在过去十年中,细胞培养和啮齿动物的广泛研究表明,姜黄素可以使肿瘤对包括阿霉素、5-FU、紫杉醇、长春新碱、美法仑、丁酸盐、顺铂、塞来昔布、长春瑞滨、吉西他滨、奥沙利铂、依托泊苷、磺丁基醚、沙利度胺和硼替佐米在内的不同化疗药物敏感。在乳腺癌、结肠癌、胰腺癌、胃癌、肝癌、血液癌、肺癌、前列腺癌、膀胱癌、宫颈癌、卵巢癌、头颈部癌和脑癌以及多发性骨髓瘤、白血病和淋巴瘤中都观察到了化疗增敏作用。类似的研究还表明,这种药物可以使多种肿瘤对包括神经胶质瘤、神经母细胞瘤、宫颈癌、表皮癌、前列腺癌和结肠癌在内的伽马射线敏感。姜黄素作为化疗增敏剂和放射增敏剂的作用也得到了广泛的研究。例如,它下调了各种生长调节途径和特定的遗传靶点,包括 NF-κB、STAT3、COX2、Akt、抗凋亡蛋白、生长因子受体和多药耐药蛋白的基因。尽管姜黄素在某些情况下可以作为肿瘤的化疗增敏剂和放射增敏剂,但它也已被证明可以保护肝脏、肾脏、口腔黏膜和心脏等正常器官免受化疗和放疗引起的毒性。姜黄素的保护作用似乎是通过其诱导 NRF2 激活和诱导抗氧化酶表达(例如血红素加氧酶-1、谷胱甘肽过氧化物酶、γ-谷氨酰半胱氨酸连接酶调节亚基和 NAD(P)H:醌氧化还原酶 1、增加谷胱甘肽(γ-谷氨酰半胱氨酸连接酶调节亚基的产物)、直接清除自由基和抑制 p300 HAT 活性来实现的。这些临床前研究有望导致临床试验,以证明这种古老的金色香料治疗癌症患者的潜力。

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