Куркумин Curcumin
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- Polyisoprenylated метилированных белка метил эстеразы является чувствительной к куркумин и overexpressed колоректального рака: последствия для химиопрофилактики и лечения.
- Concurrent inhibition of enzymatic activity and NF-Y-mediated transcription of Topoisomerase-IIα by bis-DemethoxyCurcumin in cancer cells.
- Одновременное торможение ферментативной активности NF-Y-опосредованной транскрипции Топоизомеразы-IIα бис-DemethoxyCurcumin в раковых клетках.
- Turmeric (curcumin) remedies gastroprotective action.
- Турмерик (куркума) средства правовой защиты гастропротекторные действий.
- Polymeric mixed micelles for delivery of curcumin to multidrug resistant ovarian cancer. Saxena V , Hussain MD . Author information
- Полимерные смешанные мицеллы на поставку куркумин, чтобы с множественной лекарственной устойчивостью, рак яичников.
- The role of cancer stem cells in the anti-carcinogenicity of curcumin.
- Роль раковые стволовые клетки в борьбе с Канцерогенность куркумин.
- Medicinal chemistry of the epigenetic diet and caloric restriction. Martin SL , Hardy TM , Tollefsbol TO . Author information
- Медицинская химия эпигенетических диеты и ограничения калорийности питания.
- Curcumin reduces trabecular and cortical bone in naive and lewis lung carcinoma-bearing mice. Yan L , Yee JA , Cao J . Author information
Polyisoprenylated methylated protein methyl esterase is both sensitive to curcumin and overexpressed in colorectal cancer: implications for chemoprevention and treatment. Amissah F, Duverna R, Aguilar BJ, Poku RA, Lamango NS.
Abstract Inhibition of PMPMEase, a key enzyme in the polyisoprenylation pathway, induces cancer cell death. In this study, purified PMPMEase was inhibited by the chemopreventive agent, curcumin, with a K(i) of 0.3 μM (IC50 = 12.4 μM). Preincubation of PMPMEase with 1 mM curcumin followed by gel-filtration chromatography resulted in recovery of the enzyme activity, indicative of reversible inhibition. Kinetics analysis with N-para-nitrobenzoyl-S-trans,trans-farnesylcysteine methyl ester substrate yielded K M values of 23.6 ± 2.7 and 85.3 ± 15.3 μM in the absence or presence of 20 μM curcumin, respectively. Treatment of colorectal cancer (Caco2) cells with curcumin resulted in concentration-dependent cell death with an EC50 of 22.0 μg/mL. PMPMEase activity in the curcumin-treated cell lysate followed a similar concentration-dependent profile with IC50 of 22.6 μg/mL. In colorectal cancer tissue microarray studies, PMPMEase immunoreactivity was significantly higher in 88.6% of cases compared to normal colon tissues (P < 0.0001). The mean scores ± SEM were 91.7 ± 11.4 (normal), 75.0 ± 14.4 (normal adjacent), 294.8 ± 7.8 (adenocarcinoma), and 310.0 ± 22.6 (mucinous adenocarcinoma), respectively. PMPMEase overexpression in colorectal cancer and cancer cell death stemming from its inhibition is an indication of its possible role in cancer progression and a target for chemopreventive agents. Biomed Res Int. 2013 г.; 2013:416534. doi: 10.1155/2013/416534. Epub 2013 июл 1.
Abstract Topoisomerases-IIα (TOP2A) enzyme is essential for cell viability due to its fundamental role in DNA metabolism and in chromatin organization during interphase and mitosis. TOP2A expression is finely regulated at the transcriptional level through the binding of the CCAAT-transcription factor NF-Y to its promoter. Overexpression and/or amplification of TOP2A have been observed in many types of cancers. For this reason, TOP2A is the target of the most widely successful drugs in cancer chemotherapy, such as TOP2A poisons, which stabilize TOP2A-DNA cleavage complexes and create DSBs, leading to chromosome damage and cell death. We previously reported that the Curcumin-derivative bis-DemethoxyCurcumin (bDMC) is an anti-proliferative agent that inhibits cell growth by concomitant G1/S and G2/M arrest. Here we showed that bDMC irreversibly induces DSBs in cancer cells, but not in normal cells, by targeting TOP2A activity and expression. TOP2A ablation by siRNA corroborates its contribution to apoptosis induced by bDMC. Short-term exposure to bDMC induces retention of TOP2A-DNA intermediates, while longer exposure inhibits TOP2A transcription by affecting expression and sub-cellular localization of NF-Y subunits. ChIP analysis highlighted reduced recruitment of NF-Y to TOP2A regulatory regions, concomitantly to histone deacetylation and decreased gene transcription. Our findings suggest that the dual activity of bDMC on TOP2A represents a novel therapeutic strategy to induce persistent apoptosis in cancer cells and identify NF-Y regulation as a promising approach in anti-cancer therapy. Гибель Клеток Dis. 2013 авг 8;4:e756. doi: 10.1038/cddis.2013.287. Одновременное торможение ферментативной активности NF-Y-опосредованной транскрипции Топоизомеразы-IIα бис-DemethoxyCurcumin в раковых клетках. Belluti S, Базиле V, Benatti P, Ferrari E, Marverti G, Imbriano C. Dipartimento della Vita di Scienze, Universita di Modena e Реджо-Эмилия, через Кампи-213/D, Модена 41125, Италия. Топоизомеразы-IIα (TOP2A) фермент необходим для жизнеспособность клеток благодаря своей основополагающей роли в метаболизм ДНК и хроматина в организации в течение interphase и митоз. TOP2A выражение тонко регулируется на транскрипционном уровне посредством привязки CCAAT-фактора транскрипции NF-Y, чтобы его промоутер. Гиперэкспрессия и/или усиления TOP2A наблюдались во многих типов рака. По этой причине, TOP2A является целью наиболее широко успешных препаратов в химиотерапии рака, таких как TOP2A яды, которые стабилизируют TOP2A-расщепление ДНК комплексов и создать Др, ведущих к хромосомные повреждения и гибели клеток. Ранее мы сообщали о том, что Куркумин-производные бис-DemethoxyCurcumin (bDMC) является анти-пролиферативной агент, который подавляет рост клеток при одновременном G1/S и G2/M ареста. Здесь мы показали, что bDMC необратимо индуцирует Др в раковые клетки, но не в нормальных клетках, ориентируясь на TOP2A деятельности и выражения. TOP2A абляция при siRNA подтверждает свой вклад в апоптоза, индуцированного bDMC. Краткосрочные воздействия bDMC вызывает сохранение TOP2A-ДНК полупродуктов, при более длительной экспозиции тормозит TOP2A транскрипции, влияющих на выражение и внутриклеточная локализация NF-Y субъединиц. Чип анализ подчеркнул снижению пополнения NF-Y, чтобы TOP2A регуляторных районов, совместно деацетилирование гистонов и снизился транскрипции генов. Наши исследования показывают, что двойная активность bDMC на TOP2A представляет новую терапевтическую стратегию, чтобы вызвать стойкие апоптоз в раковых клетках и определить NF-Y регулирования в качестве перспективного подхода в противораковой терапии. Pharmacogn Rev. 2013 Jan;7(13):42-6. doi: 10.4103/0973-7847.112843. Turmeric (curcumin) remedies gastroprotective action. Yadav SK, Sah AK, Jha RK, Sah P, Shah DK.
The purpose of this review is to summarize the pertinent literature published in the present era regarding the antiulcerogenic property of curcumin against the pathological changes in response to ulcer effectors (Helicobacter pylori infection, chronic ingestion of non-steroidal anti-inflammatory drugs, and exogenous substances). The gastrointestinal problems caused by different etiologies was observed to be associated with the alterations of various physiologic parameters such as reactive oxygen species, nitric oxide synthase, lipid peroxidation, and secretion of excessive gastric acid. Gastrointestinal ulcer results probably due to imbalance between the aggressive and the defensive factors. In 80% of the cases, gastric ulcer is caused primarily due to the use of non-steroidal anti-inflammatory category of drug, 10% by H. pylori, and about 8-10% by the intake of very spicy and fast food. Although a number of antiulcer drugs and cytoprotectants are available, all these drugs have side effects and limitations. In the recent years a widespread search has been launched to identify new antiulcer drugs from synthetic and natural resources. An Indian dietary derivative (curcumin), a yellow pigment found in the rhizome of Curcuma longa, has been widely used for the treatment of several diseases. Epidemiologically, it was suggested that curcumin might reduce the risk of inflammatory disorders, such as cancer and ulcer. These biological effects are attributed to its anti-inflammatory and antioxidant activities. It can, therefore, be reported from the literature that curcumin PRevents gastrointestinal-induced ulcer and can be recommended as a novel drug for ulcer treatment. Pharmacogn Rev. 2013 янв.; 7(13):42-6. doi: 10.4103/0973-7847 .112843. Турмерик (куркума) средства правовой защиты гастропротекторные действий. Ядав SK, Sah АК, Джа РК, " P", " шах-DK. Кафедра Челюстно-лицевой Хирургии, Читван Медицинский колледж (P) Ltd., Бхаратпур, Читван, Непал. Целью данного обзора является обобщение соответствующей литературы, изданной в настоящее время в отношении antiulcerogenic свойства куркумина против патологических изменений в ответ на язва эффекторов (Helicobacter pylori-инфекции, хронические приеме нестероидных противовоспалительных препаратов, экзогенных веществ). В желудочно-кишечные заболевания различной этиологии, вызванных, как было замечено, связанные с изменениями различных физиологических параметров, таких как активные формы кислорода, оксид азота-синтаза, перекисное окисление липидов и чрезмерную секрецию желудочной кислоты. Желудочно-кишечные язвы результаты, вероятно, из-за дисбаланса между агрессивных и защитных факторов. В 80% случаев язвенная болезнь желудка связано, прежде всего, благодаря использованию нестероидных противовоспалительных категории наркотиков, 10% - H. pylori, и около 8-10% потребление очень острые и фаст-фуд. Хотя ряд противоязвенных и cytoprotectants доступны, все эти препараты имеют побочные эффекты и ограничения. В последние годы широкое поиск был начат с целью выявления новых противоязвенных из синтетических и природных ресурсов. Индийский диетическое производные (куркума), желтого пигмента содержится в корневище Curcuma longa, широко используется для лечения ряда заболеваний. С эпидемиологической точки зрения, было высказано мнение, что куркумин может снизить риск развития воспалительных заболеваний, таких как рак и болезнь. Эти биологические эффекты связаны с его противовоспалительным и антиоксидантным деятельности. Она может, следовательно, быть сообщено из литературы, что куркумин Предотвращает желудочно-индуцированных язв желудка и может быть рекомендован в качестве новых препаратов для лечения язвы. J Biomed Nanotechnol. 2013 Jul;9(7):1146-54. Polymeric mixed micelles for delivery of curcumin to multidrug resistant ovarian cancer. Saxena V, Hussain MD. Author information
Abstract The biggest challenge for the treatment of multidrug resistance cancer is to deliver high concentration of anticancer drugs specifically to cancer cells for longer period of time. Poloxamers and D-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) are known inhibitors of P-glycoprotein. Mixed micelles prepared from Poloxamer 407 and TPGS may increases the therapeutic efficacy of drug by delivering high concentration of drug inside the cells and inhibition of P-gp. Curcumin (CUR) is a naturally derived novel anticancer agent but poor solubility limited its clinical use. In this study, we have developed Poloxamer 407 and TPGS mixed micelle encapsulating CUR for treatment of multidrug-resistant ovarian cancer. CUR-loaded Poloxamer 407/TPGS mixed micelles were prepared by thin film hydration method and their physicochemical properties were characterized. Cellular uptake and in vitro cytotoxicity of the CUR-loaded Poloxamer 407/TPGS mixed micelles were studied in multidrug-resistant ovarian cancer (NCI/ADR-RES) cells. The diameter of CUR-loaded Poloxamer 407/TPGS mixed micelles was about 21.4 +/- 0.3 nm and a zeta potential of -11.56 +/- 0.7 mV. The encapsulation efficiency of CUR was ranged from 95-86% with drug loading was about 1-9%. Differential scanning calorimetry and X-ray powder diffraction studies confirmed that CUR was encapsulated by the polymers. The in vitro release studies showed that mixed micelles sustained the release of CUR for more than 9 days. Results from cellular uptake studies indicated that CUR-loaded Poloxamer 407/TPGS mixed micelles had increased cellular uptake of CUR in NCI/ADR-RES cells. Cytotoxicity of CUR-loaded Poloxamer 407/TPGS mixed micelles was found to be 3 folds more than free CUR after 48 of incubations. Conclusion: This study suggests that Poloxamer 407/TPGS mixed micelles might be a suitable nanocarrier for curcumin to treat multidrug resistant ovarian cancer. J Biomed Nanotechnol. 2013 июля;9(7):1146-54.
Abstract Many cancers contain cell subpopulations that display characteristics of stem cells. These cells are characterised by their ability to self-renew, form differentiated progeny and develop resistance to chemotherapeutic strategies. Cancer stem cells may utilise many of the same signalling pathways as normal stem cells including Wnt, Notch and Hedgehog. The dietary agent curcumin exerts a plethora of anti-carcinogenic effects both in vitro and in vivo, and can also inhibit many of the signalling pathways associated with stem cell biology. Emerging evidence suggests that curcumin can exert its anti-carcinogenic activity via targeting cancer stem cells through the disruption of stem cell signalling pathways. In this review we summarise the ability of curcumin to interfere with signalling pathways Wnt, Hedgehog, Notch, Signal Transducers and Activator (STAT) and interleukin-8, and report curcumin-induced changes in function and properties of cancer stem cells. We present evidence that the effects of curcumin on cancer stem cells mediate, or contribute to, its anti-carcinogenic activity. Мол Nutr Пищи. 2013 Sep;57(9):1630-7. doi: 10.1002/mnfr.201300120. Epub 2013 июл 31.
Abstract The pronounced effects of the epigenetic diet (ED) and caloric restriction (CR) have on epigenetic gene regulation have been documented in many pre-clinical and clinical studies. Understanding epigenetics is of high importance because of the concept that external factors such as nutrition and diet may possess the ability to alter gene expression without modifying the DNA sequence. The ED introduces bioactive medicinal chemistry compounds such as sulforaphane (SFN), curcumin (CCM), epigallocatechin gallate (EGCG) and resveratrol (RSV) that are thought to aid in extending the human lifespan. CR, although similar to ED in the target of longevity, mildly reduces the total daily calorie intake while concurrently providing all beneficial nutrients. Both CR and ED may act as epigenetic modifiers to slow the aging process through histone modification, DNA methylation, and by modulating microRNA expression. CR and ED have been proposed as two important mechanisms that modulate and potentially slow the progression of age-related diseases such as cardiovascular disease (CVD), cancer, obesity, Alzheimer's and osteoporosis to name a few. While many investigators have examined CR and ED as separate entities, this review will primarily focus on both as they relate to age-related diseases, their epigenetic effects and their medicinal chemistry. Curr Chem-Med. 2013 года;20(32):4050-9.
Abstract The present study investigated the effects of curcumin on bone microstructure in non-tumor-bearing and Lewis lung carcinoma-(LLC)-bearing female C57BL/6 mice. Morphometric analysis showed that dietary supplementation with curcumin (2% or 4%) significantly reduced the bone volume to total volume ratio, connectivity density and trabecular number, and significantly increased the structure model index (an indicator of the plate- and rod-like geometry of trabecular structure) and trabecular separation in vertebral bodies compared to controls in both non-tumor-bearing and LLC-bearing mice. Similar changes in trabecular bone were observed in the femoral bone in curcumin-fed mice. Curcumin significantly reduced the cortical bone area to total area ratio and cortical thickness in femoral mid-shaft, but not in vertebral bodies, in both non-tumor-bearing and LLC-bearing mice. Curcumin feeding reduced plasma concentrations of osteocalcin and increased tartrate-resistant acid phosphate 5b in mice regardless of the presence of LLC, indicating that curcumin disrupts the balance of bone remodeling. Our results demonstrated that curcumin reduced the trabecular bone volume and cortical bone density. The skeleton is a favored site of metastasis for many types of cancers, and curcumin has been investigated in clinical trials in patients with cancer for its chemopreventive effects. Our results suggest the possibility of a combined effect of cancer-induced osteolysis and curcumin-stimulated bone loss in patients using curcumin. The assessment of bone structural changes should be considered for those who participate in curcumin clinical trials to determine its effects on skeleton health, particularly for those with advanced malignancies. Противораковых Res. 2013 авг.; 33(8):3153-61. жүктеу/скачать 2.05 Mb. Достарыңызбен бөлісу:
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