29.5.08

La curcuma tiene efectos protectores en modelos de obesidad y diabetes

La obesidad es uno de los mayores factores de riesgo para el desarrollo de la diabetes de tipo 2, y en la actualidad se sabe que ambas condiciones poseen componentes inflamatorios asociados a sus patofisiologías. Este grupo del centro de investigación de la Universidad de Columbia en Nueva York ha evaluado la hipótesis de que el compuesto polifenólico curcumina, componente principal del turmérico (Curcuma Longa), usado desde hace miles de años en medicina ayurvédica y china y de conocidas y potentes propiedades antiinflamatorias y antioxidantes, mejoraría la diabetes y la inflamación en modelos de roedor de obesidad resistente a insulina. Este grupo encontró que la mezcla de curcumina que fue administrada a los ratones, mejoró la diabetes en ratones obesos con obesidad inducida por una dieta rica en grasas, y también en ratones machos deficientes en el receptor de la leptina. Los parámetros evaluados fueron los niveles de glucosa, la tolerancia a la insulina, y el porcentaje de hemoglobina glicosilada A1c. El tratamiento con curcumina, además, redujo la infiltración de los macrófagos en el tejido adiposo blanco, disminuyó la producción de adiponectina, la actividad NF-kappaB hepática, hepatomegalia, y marcadores de inflamación hepática. Este grupo de Nueva York concluye que la curcumina, ingerida por vía oral, revierte muchas de las alteraciones metabólicas e inflamatorias asociadas con la obesidad, y mejora el control glicémico en modelos de diabetes de tipo 2. Por ello afirman que está justificada la investigación de este compuesto y compuestos relacionados como terapia adyuvante para el tratamiento de la diabetes de tipo 2 en el hombre.

Endocrinology. 2008 Apr 10. [Epub ahead of print]Click here to read Links
Dietary Curcumin Significantly Improves Obesity-Associated Inflammation and Diabetes in Mouse Models of Diabesity.
Weisberg SP, Leibel R, Tortoriello DV.

Diabetes and Endocrinology Research Center, Columbia University, New York, New York; Sher Institute for Reproductive Medicine, New York, New York.

Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. We tested the hypothesis that the plant polyphenolic compound curcumin, which is known to exert potent anti-inflammatory and anti-oxidant effects, would ameliorate diabetes and inflammation in murine models of insulin-resistant obesity. We found that dietary curcumin admixture ameliorated diabetes in high-fat diet induced obese (DIO) and leptin-deficient ob/ob male C57BL/6J mice as determined by glucose and insulin tolerance testing and hemoglobin A1c percentages. Curcumin treatment also significantly reduced macrophage infiltration of white adipose tissue, increased adipose tissue adiponectin production, and decreased hepatic nuclear NF-kappaB activity, hepatomegaly, and markers of hepatic inflammation. We therefore conclude that orally ingested curcumin reverses many of the inflammatory and metabolic derangements associated with obesity and improves glycemic control in mouse models of type 2 diabetes. This or related compounds warrant further investigation as novel adjunctive therapies for type 2 diabetes in man.

27.5.08

Potencial terapéutico de la hierba china Huang-Qin (Scutellaria baicalensis Georgi) en el tratamiento de malignidades hematológicas.

Las hierbas se han utilizado en la medicina Tradicional China durante siglos. Sin embargo, sus mecanismos curativos son mayoritariamente desconocidos. En este estudio, un grupo de investigación de la ciudad alemana de Heidelberg, perteneciente al “Centro alemán de investigación sobre cáncer”, muestra que la wogonina, derivada de la planta tradicional china “Huang-Qin” (cuyo nombre latín es Scutellaria baicalensis Georgi), induce apoptosis –muerte celular programada- en células T humanas malignas en experimentos in vitro. Además, el tratamiento con este compuesto impide el crecimiento de células T malignas de leucemia, cuando éstas se implantan a un ratón
–se habla de “xenoimplante” por tratarse de especies, hombre y ratón, diferentes-. Es muy importante destacar que la wogonina no muestra apenas toxicidad en linfocitos T de donantes sanos. Por lo tanto, estos investigadores muestran que el efecto de este compuesto, obtenido de la planta china “Huang-Qin”, es selectivo, siendo principalmente tóxico para las células T malignas. También descubren que este efecto selectivo se debe a que las células T malignas son más sensibles a la oxidación, y también se debe a que, en estas células, la elevación de calcio derivada de esta oxidación aumentada es asimismo mucho mayor, lo cual origina efectos tóxicos específicos en estas células. Este estudio, publicado en la prestigiosa revista “Blood”, concluye que la wogonina podría utilizarse para tratar malignidades hematológicas.


Blood. 2008 Feb 15;111(4):2354-63. Epub 2007 Dec 10.Click here to read Links
Wogonin preferentially kills malignant lymphocytes and suppresses T-cell tumor growth by inducing PLCgamma1- and Ca2+-dependent apoptosis.
Baumann S, Fas SC, Giaisi M, Müller WW, Merling A, Gülow K, Edler L, Krammer PH, Li-Weber M.

Tumorimmunology Program (D030), German Cancer Research Center, Heidelberg, Germany.

Herbs have successfully been used in traditional Chinese medicine for centuries. However, their curative mechanisms remain largely unknown. In this study, we show that Wogonin, derived from the traditional Chinese medicine Huang-Qin (Scutellaria baicalensis Georgi), induces apoptosis in malignant T cells in vitro and suppresses growth of human T-cell leukemia xenografts in vivo. Importantly, Wogonin shows almost no toxicity on T lymphocytes from healthy donors. Wogonin induces prolonged activation of PLCgamma1 via H(2)O(2) signaling in malignant T cells, which leads to sustained elevation of cytosolic Ca(2+) in malignant but not normal T cells. Subsequently, a Ca(2+) overload leads to disruption of the mitochondrial membrane. The selective effect of Wogonin is due to its differential regulation of the redox status of malignant versus normal T cells. In addition, we show that the L-type voltage-dependent Ca(2+) channels are involved in the intracellular Ca(2+) mobilization in T cells. Furthermore, we show that malignant T cells possess elevated amounts of voltage-dependent Ca(2+) channels compared with normal T cells, which further enhance the cytotoxicity of Wogonin for malignant T cells. Taken together, our data show a therapeutic potential of Wogonin for the treatment of hematologic malignancies.

Sustancias naturales que inhiben la angiogénesis: una fuente potencial para la investigación de nuevos agentes para tratar el cáncer

Un enfoque integrativo para tratar a los pacientes con cáncer debe tener como objetivo las vías múltiples bioquímicas y fisiológicas que favorecen el desarrollo del tumor y deben asimismo minimizar la toxicidad en tejidos sanos. La angiogénesis es un proceso clave en el desarrollo del cáncer. Muchos agentes naturales que inhiben la angiogénesis manifiestan también otras actividades anticancerosas. Este artículo se centra en los productos que tienen una gran actividad antiangiogénica como: Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumina), Scutellaria baicalensis (Chinese skullcap), resveratrol y proantocianidina (extracto de pepita de uva), Magnolia officinalis (árbol de magnolia china), Camellia sinensis (té verde), Ginkgo biloba, quercetina, Poria cocos, Zingiber officinalis (gengibre), Panax ginseng, Rabdosia rubescens hora (Rabdosia), y algunas hierbas chinas. Este artículo también describe algunas de las otras acciones de estos agentes que pueden inhibir la progresión tumoral y reducir el riesgo de metástasis.

Curr Oncol. 2006 Feb;13(1):14-26.Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer Sagar SM, Yance D, Wong RK. Juravinski Cancer Centre and McMaster University (Department of Medicine), Hamilton, Ontario.

An integrative approach for managing a patient with cancer should target the multiple biochemical and physiologic pathways that support tumour development and minimize normal-tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The present article focuses on products that have a high degree of anti-angiogenic activity, but it also describes some of the many other actions of these agents that can inhibit tumour progression and reduce the risk of metastasis. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclooxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose-response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as adaptogens, potentially enhancing the efficacy of the conventional therapies.

26.5.08

La decocción de Peony-Glycyrrhiza es más segura que la bromocriptina para la inhibición de la secreción de prolactina.

J Clin Psychopharmacol. 2008 Jun;28(3):264-370.Click here to read Links A Randomized, Crossover Comparison of Herbal Medicine and Bromocriptine Against Risperidone-Induced Hyperprolactinemia in Patients With Schizophrenia. Yuan HN, Wang CY, Sze CW, Tong Y, Tan QR, Feng XJ, Liu RM, Zhang JZ, Zhang YB, Zhang ZJ.

*Laboratory of Clinical Psychopharmacology, Beijing Anding Hospital, Capital Medical University, Beijing; †School of Chinese Medicine, The University of Hong Kong, Hong Kong; and ‡Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China.

Hyperprolactinemia is a common adverse effect that occurs as a result of antipsychotic therapies, which often results in discontinuation. Empirical evidence has shown that some herbal medicines have suppressive effects on prolactin (PRL) hyperactivities. This study was designed to compare the herbal preparation called Peony-Glycyrrhiza Decoction (PGD) with bromocriptine (BMT), a dopamine agonist widely used for PRL-secreting disorders, in the treatment of risperidone-induced hyperprolactinemia. Twenty schizophrenic women who were under risperidone maintenance treatment, diagnosed with hyperprolactinemia (serum PRL levels >50 mug/L), and currently experiencing oligomenorrhea or amenorrhea were selected for the study. Subjects were randomized to additional treatment with PGD (45 g/d) followed by BMT (5 mg/d) or BMT followed by PGD at the same doses for 4 weeks each, with an interval of 4-week washout period between 2 treatment sessions. The severity of psychotic symptoms, adverse events, serum PRL, estradiol, testosterone, and progesterone levels were examined at baseline and end point. Peony-Glycyrrhiza Decoction treatment produced a significant baseline-end point decrease in serum PRL levels, without exacerbating psychosis and changing other hormones, and the decreased amplitudes were similar to those of BMT (24% vs 21%-38%). Moreover, there was a significantly greater proportion of patients during PGD treatment than BMT treatment showing improvements on adverse effects associated with hyperprolactinemia (56% vs 17%, P = 0.037). These results suggest that the herbal therapy can yield additional benefits while having comparable efficacy in treating antipsychotic-induced hyperprolactinemia in individuals with schizophrenia.

25.5.08

La planta china medicinal Curculigo orchioides previene la osteoporosis.

Las medicinas naturales derivadas de las plantas han recibido atención para la prevención y el tratamiento de la osteoporosis. Esto se debe a sus características únicas, ya que se pueden realizar tratamientos más largos, comparado con las sustancias fabricadas de manera sintética, que muestran más efectos adversos.
Curculigo orchioides tiene una larga historia en el tratamiento de la osteoporosis menopáusica en la medicina tradicional china. El estudio mostrado aquí se diseñó para investigar los efectos protectores del extracto etanólico de Curculigo orchioides en la pérdida ósea inducida por ovarectomia en ratas. Como conclusión, el extracto etanólico de Curculigo orchioides tuvo un efecto protector en la pérdida osea en este modelo, mediante la inhibición de la reabsorción ósea y el aumento de los niveles plasmáticos de fósforo y cálcio, sin afectar a la formación ósea. Por ello, Curculigo orchioides puede ser considerada una planta con propiedades potenciales para el tratamiento de la osteoporosis, aunque se necesitan más estudios para conocer con claridad los constituyentes químicos implicados y su mecanismo de acción.

Maturitas. 2008 May 9. Curculigo orchioides, a traditional Chinese medicinal plant, prevents bone loss in ovariectomized rats. Cao DP, Zheng YN, Qin LP, Han T, Zhang H, Rahman K, Zhang QY.

Department of Pharmacognosy, School of Pharmacy, Second Military Medical University, Shanghai 200433, People's Republic of China; College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, People's Republic of China.

OBJECTIVE: Natural medicines derived from plants have aroused increasing interest in the prevention and treatment of osteoporosis. This is due to their unique characteristics as these are more suitable for long-term use compared with synthesized chemicals and have apparently fewer adverse effects. Curculigo orchioides (CO) has a long history in the treatment of postmenopausal osteoporosis in traditional Chinese medicine. The present study was designed to investigate the protective effects of ethanol extracts of CO on ovariectomy-induced bone loss. METHODS: Sixty female (4.5-month-old) Sprague-Dawley rats were assigned to sham and OVX groups. The OVX rats were further divided into five subgroups treated respectively, with vehicle, nylestriol (1mg/kg, i.g.) and CO extract (0.5, 1.0, and 2.0g/kg, i.g.) for 12 weeks. Bone mineral density (BMD) and bone mineral content (BMC) were measured by peripheral quantitative computerized tomography (pQCT) densitometry. Serum phosphorus, calcium, ACTH, corticosterone, deoxypyridinoline crosslinks to creatinine ratio (DPD/Cr), alkaline phosphate (ALP), tartrate-resistant acid phosphatase (TRAP), osteoprotegerin (OPG), IL-6, and TNF-alpha were also determined. RESULTS: Administration of CO extract prevented bone loss in the trabecular bone of the tibia in ovariectomized rats without affecting the weight of the body and the uterus, and increased serum phosphorus, calcium, and OPG levels, decreased serum DPD/Cr, TRAP, ACTH, and corticosterone levels, but did not alter serum TNF-alpha, IL-6, and ALP levels in ovariectomized rats. CONCLUSION: CO ethanol extract has a definite protective effect on bone loss in ovariectomized rats by inhibiting bone resorption and increasing serum phosphorus and calcium levels, without affecting bone formation. Therefore, CO can be considered a potential antiosteoporosis herbal plant, although more studies are needed to clarify its real potential chemical constituents and their mechanism of action.

21.5.08

La formula china Realgar-Indigo naturalis muestra eficacia en el tratamiento de la leucemia promielocítica

Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4826-31. Epub 2008 Mar 14.Click here to read Links
Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia.
Wang L, Zhou GB, Liu P, Song JH, Liang Y, Yan XJ, Xu F, Wang BS, Mao JH, Shen ZX, Chen SJ, Chen Z.

State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 197 Rui Jin Road II, Shanghai 200025, China.

To enhance therapeutic efficacy and reduce adverse effects, practitioners of traditional Chinese medicine (TCM) prescribe a combination of plant species/minerals, called formulae, based on clinical experience. Nearly 100,000 formulae have been recorded, but the working mechanisms of most remain unknown. In trying to address the possible beneficial effects of formulae with current biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has been proven to be very effective in treating human acute promyelocytic leukemia (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and tanshinone IIA (T) as major active ingredients, respectively. Here, we report that the ATI combination yields synergy in the treatment of a murine APL model in vivo and in the induction of APL cell differentiation in vitro. ATI causes intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor alpha (RARalpha) oncoprotein, stronger reprogramming of myeloid differentiation regulators, and enhanced G(1)/G(0) arrest in APL cells through hitting multiple targets compared with the effects of mono- or biagents. Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates the transportation of A into APL cells, which in turn enhances A-mediated PML-RARalpha degradation and therapeutic efficacy. Our data also indicate A as the principal component of the formula, whereas T and I serve as adjuvant ingredients. We therefore suggest that dissecting the mode of action of clinically effective formulae at the molecular, cellular, and organism levels may be a good strategy in exploring the value of traditional medicine.

Efectos antitumorales de Astragalus membranaceus in vivo e in vitro

Cancer Lett. 2007 Jul 8;252(1):43-54. Epub 2007 Jan 16.Click here to read Links
In vitro and in vivo anti-tumor effects of Astragalus membranaceus.
Cho WC, Leung KN.

Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, People's Republic of China. chocs@ha.org.hk

Astragalus membranaceus, a commonly used Chinese medicinal plant, has been shown to be capable of restoring the impaired T cell functions in cancer patients. In this study, the in vitro and in vivo anti-tumor effects of A. membranaceus were investigated. Five bioactive fractions were isolated from the root of A. membranaceus, the fraction designated as AI was found to be the most potent among the five fractions with respect to its mitogenicity on murine splenocytes. Besides investigating the cytostatic effect of AI, its activities on macrophage function, tumor necrosis factor production, induction of lymphokine-activated killer cell and tumor cell differentiation were also examined. The macrophage-like tumors and the myeloid tumors were found to be more sensitive to the cytostatic activity of AI, whereas the fibroblast-like tumors and the mouse Ehrlich ascites tumor appeared to be relatively resistant. Moreover, AI could effectively suppress the in vivo growth of syngeneic tumor in mice. Results showed that murine macrophage pretreated with AI had increased in vitro and in vivo cytostatic activities towards MBL-2 tumor. AI could also act as a priming agent for tumor necrosis factor production in tumor-bearing mice. Preincubation of mouse splenocytes with AI could induce in vitro lymphokine-activated killer-like activity towards WEHI-164 cell. Furthermore, AI was able to induce monocytic differentiation of both human and murine cells in vitro. AI administered in vivo could even partially restore the depressed mitogenic response in tumor-bearing mice. Collectively, the results showed that A. membranaceus could exhibit both in vitro and in vivo anti-tumor effects, which might be achieved through activating the anti-tumor immune mechanism of the host.

6.5.08

El estrés repetido altera el metabolismo

Endocrinology. 2008 Mar 11 [Epub ahead of print]Click here to read Links
Hypermetabolic syndrome as a consequence of repeated psychological stress in mice.
Depke M, Fusch G, Domanska G, Geffers R, Völker U, Schuett C, Kiank C.

Interfaculty Institute of Genetics and Functional Genomics (U.V.), Institute of Immunology and Transfusion Medicine, Department of Immunology (C.S., G.D., C.K.), Department of Neonatology and Pediatric Intensive Care Medicine (G.F.); Ernst-Moritz-Arndt-University Greifswald, Germany; Department of Mucosal Immunity, Helmholtz-Centre for Infection Research, Braunschweig, Germany (R.G.).

Stress is a powerful modulator of neuroendocrine, behavioral and immunological functions. After 4.5 days of repeated combined acoustic and restraint stress as a murine model of chronic psychological stress severe metabolic dysregulations became detectable in female BALB/c mice. Stress-induced alterations of metabolic processes that were found in a hepatic mRNA expression profiling were verified by in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome with severe loss of lean body mass, hyperglycemia, dyslipidemia, increased amino acid turn-over, and acidosis. This was associated with hypercortisolism, hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a single acute stress exposure changes in expression of metabolic genes were much less pronounced and predominantly confined to gluconeogenesis, probably indicating that metabolic disturbances might be initiated already early but will only manifest in repeatedly stressed mice. Thus, in our murine model, repeated stress caused severe metabolic dysregulations leading to a drastic reduction of the individual's energy reserves. Under such circumstances stress may further reduce the ability to cope with new stressors such as infection or cancer.

Dieta cetogénica para el cáncer

BMC Cancer. 2008 Apr 30;8(1):122 [Epub ahead of print]Click here to read Links
Growth of human gastric cancer cells in nude mice is delayed by a ketogenic diet supplemented with omega-3 fatty acids and medium-chain triglycerides.
Otto C, Kaemmerer U, Illert B, Muehling B, Pfetzer N, Wittig R, Voelker HU, Thiede A, Coy JF.

ABSTRACT: BACKGROUND: Among the most prominent metabolic alterations in cancer cells are the increase in glucose consumption and the conversion of glucose to lactic acid via the reduction of pyruvate even in the presence of oxygen. This phenomenon, known as aerobic glycolysis or the Warburg effect, may provide a rationale for therapeutic strategies that inhibit tumour growth by administration of a ketogenic diet with average protein but low in carbohydrates and high in fat enriched with omega-3 fatty acids and medium-chain triglycerides (MCT). METHODS: Twenty-four female NMRI nude mice were injected subcutaneously with tumour cells of the gastric adenocarcinoma cell line 23132/87. The animals were then randomly split into two feeding groups and fed either a ketogenic diet (KD group; n=12) or a standard diet (SD group; n=12) ad libitum. Experiments were ended upon attainment of the target tumor volume of 600 mm3 to 700 mm3. The two diets were compared based on tumour growth and survival time (interval between tumour cell injection and attainment of target tumour volume). RESULTS: The ketogenic diet was well accepted by the KD mice. The tumour growth in the KD group was significantly delayed compared to that in the SD group. Tumours in the KD group reached the target tumour volume at 34.2 +/- 8.5 days versus only 23.3 +/- 3.9 days in the SD group. After day 20, tumours in the KD group grew faster although the differences in median tumour growth continued significantly. Importantly, they revealed significantly larger necrotic areas than tumours of the SD group and the areas with vital tumour cells appear to have had fewer vessels than tumours of the SD group. Viable tumour cells in the border zone surrounding the necrotic areas of tumours of both groups exhibited a glycolytic phenotype with expression of glucose transporter-1 and transketolase-like 1 enzyme. CONCLUSIONS: Application of an unrestricted ketogenic diet enriched with omega-3 fatty acids and MCT delayed tumour growth in a mouse xenograft model. Further studies are needed to address the impact of this diet on other tumour-relevant functions such as invasive growth and metastasis.

Nutr Metab (Lond). 2007 Feb 21;4:5.Click here to read Click here to read Links
The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer.
Zhou W, Mukherjee P, Kiebish MA, Markis WT, Mantis JG, Seyfried TN.

Department of Biology, Boston College, Chestnut Hill, USA. zhouwb@bc.edu

BACKGROUND: Malignant brain cancer persists as a major disease of morbidity and mortality in adults and is the second leading cause of cancer death in children. Many current therapies for malignant brain tumors fail to provide long-term management because they ineffectively target tumor cells while negatively impacting the health and vitality of normal brain cells. In contrast to brain tumor cells, which lack metabolic flexibility and are largely dependent on glucose for growth and survival, normal brain cells can metabolize both glucose and ketone bodies for energy. This study evaluated the efficacy of KetoCal, a new nutritionally balanced high fat/low carbohydrate ketogenic diet for children with epilepsy, on the growth and vascularity of a malignant mouse astrocytoma (CT-2A) and a human malignant glioma (U87-MG). METHODS: Adult mice were implanted orthotopically with the malignant brain tumors and KetoCal was administered to the mice in either unrestricted amounts or in restricted amounts to reduce total caloric intake according to the manufacturers recommendation for children with refractory epilepsy. The effects KetoCal on tumor growth, vascularity, and mouse survival were compared with that of an unrestricted high carbohydrate standard diet. RESULTS: KetoCal administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet. The restricted KetoCal diet reduced plasma glucose levels while elevating plasma ketone body (beta-hydroxybutyrate) levels. Tumor microvessel density was less in the calorically restricted KetoCal groups than in the calorically unrestricted control groups. Moreover, gene expression for the mitochondrial enzymes, beta-hydroxybutyrate dehydrogenase and succinyl-CoA: 3-ketoacid CoA transferase, was lower in the tumors than in the contralateral normal brain suggesting that these brain tumors have reduced ability to metabolize ketone bodies for energy. CONCLUSION: The results indicate that KetoCal has anti-tumor and anti-angiogenic effects in experimental mouse and human brain tumors when administered in restricted amounts. The therapeutic effect of KetoCal for brain cancer management was due largely to the reduction of total caloric content, which reduces circulating glucose required for rapid tumor growth. A dependency on glucose for energy together with defects in ketone body metabolism largely account for why the brain tumors grow minimally on either a ketogenic-restricted diet or on a standard-restricted diet. Genes for ketone body metabolism should be useful for screening brain tumors that could be targeted with calorically restricted high fat/low carbohydrate ketogenic diets. This preclinical study indicates that restricted KetoCal is a safe and effective diet therapy and should be considered as an alternative therapeutic option for malignant brain cancer.

Fitoterapia en el cancer: el papel de los flavonoides a nivel celular.

Este equipo de investigación de la India redacta en este artículo las propiedades de los flavonoides en la lucha contra el cáncer.

Algunos elementos de la dieta, como la fruta, poseen una gama de flavonoides con una estructura química única y actividades biológicas diversas relevantes para el cáncer. Flavonoide (del latín flavus, "amarillo") es el término genérico con que se identifica a una serie de metabolitos secundarios de las plantas. Los flavonoides se biosintetizan en todas las plantas (taxón Embryophyta y también en algunas algas Charophyta). Los flavonoides son sintetizados en el citoplasma y luego migran hacia su destino final en las vacuolas celulares. Cumplen funciones metabólicas importantes en las plantas, Numerosos estudios epidemiológicos han validado la relación inversa entre el consumo de flavonoides y el riesgo de cáncer. Los flavonoides poseen efectos supresores del cáncer. Los flavonoides modulan varios enzimas de la familia citocromo P450 (CYPs). Los flavonoides secuestran especies reactivas formadas por los carcinógenos e inducen varios enzimas CYPs. Asimismo, regulan enzimas de fase II, relacionados con la biotransformación xenobiótica y con la microflora en el colon. Como la familia de enzimas citocromo P450, P-gp y enzimas de fase-II están relacionados con el metabolismo de medicamentos y con los procesos de carcinogénesis química, la interacción de los flavonoides con estos sistemas es muy prometedora por sus efectos terapéuticos potenciales. El papel de los flavonoides también incluye la inhibición de la activación de procarcinógenos, la inhibición de la proliferación de las células cancerosas, muerte celular selectiva de las células por apoptosis, inhibición de la metástasis y angiogénesis, activación de la respuesta inmune contra las células cancerosas, modulación de la cascada inflamatoria y modulación de la resistencia a fármacos. Estos efectos han extendido los objetivos de la terapia contra el cáncer, de la erradicación de las células afectadas al control del fenotipo canceroso.


Phytother Res. 2008 May;22(5):567-77.Click here to read Links
Cancer phytotherapeutics: role for flavonoids at the cellular level.
Kale A, Gawande S, Kotwal S.

University Department of Biochemistry, RTM Nagpur University, Nagpur 440033, India.

Dietary foods and fruits possess an array of flavonoids with unique chemical structure and diverse bioactivities relevant to cancer. Numerous epidemiological studies have validated the inverse relation between the consumption of flavonoids and the risk of cancer. Flavonoids possess cancer blocking and suppressing effects. Flavonoids modulate various CYPs involved in carcinogen activation and scavenging reactive species formed from carcinogens by CYP-mediated reactions. They induce biosynthesis of several CYPs. They are involved in the regulation of enzymes of phase-II responsible for xenobiotic biotransformation and colon microflora. Since cytochromes P450, P-gp and phase-II enzymes are involved in the metabolism of drugs and in the processes of chemical carcinogenesis, interactions of flavonoids with these systems hold great promise for their therapeutic potential. The role of flavonoids also includes the inhibition of activation of pro-carcinogens, inhibition of proliferation of cancer cells, selective death of cancer cells by apoptosis, inhibition of metastasis and angiogenesis, activation of immune response against cancer cells, modulation of the inflammatory cascade and the modulation of drug resistance. This has greatly extended the goal of cancer therapy from eradicating the affected cells to control of the cancer phenotype. Phytotherapy is being used in combination with other therapies as phytonutrients have been shown to work by nutrient synergy.