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19 septiembre 2014 5 19 /09 /septiembre /2014 21:42

 

Honokiol has shown pro-apoptotic effects in glioblastome multiforme cells melanoma, sarcoma, myeloma, leukemia, bladder, lung, prostate, oral squamous cell carcinoma

 

El honokiol de corteza de magnolia ha mostrado efectos pro-apoptóticos en células malignas del glioblastoma multiforme, y también del melanoma, sarcoma, mieloma, leucemia, cánceres de vejiga, pulmón, próstata y carcinoma oral de células escamosas

 

El honokiol es un compuesto polifenólico extraído y purificado a partir de corteza de magnolia. Tradicionalmente, se ha utilizado en la medicina china y japonesa para el tratamiento de problemas digestivos, ansiedad y cardiopatías. Eestudios en animales muestran que el honokiol es muy eficaz en atacar varias líneas celulares de cáncer, y el compuesto de la planta utiliza varias vías para detener el cáncer en sus vías metabólicas malignas.

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Las células cancerosas utilizan numerosas tácticas para evitar la detección por el sistema inmunológico del cuerpo. Las siguientes son algunas de las formas en que las células cancerosas prosperan: (1) inhiben el proceso de la muerte celular programada (apoptosis), un proceso natural que está ausente en las células cancerosas, lo que permite el crecimiento celular no regulado; (2) las "células madre" (steamcells) del cáncer se auto-renuevan y produce progenie diversa, que se resiste a la quimioterapia y la radiación; y (3) la formación de vasos sanguíneos dismórfico (angiogénesis maligna o angiogénesis del cáncer), permite que las células cancerígenas se propagen (hagan metástasis).

El compuesto polifenólico HONOKIOL tiene una amplia gama de aplicaciones que se dirigen a los mecanismos específicos que las células cancerosas emplean con el fin de crecer y propagarse en el interior del cuerpo. Sus propiedades contra el cáncer incluyen:

 

Pocos fármacos atraviesan la barrera hematoencefálica (BBB). La barrera hematoencefálica es una membrana semi-permeable, altamente selectiva; que separa el líquido especializado del cerebro del sistema circulatorio. Afortunadamente, el honokiol es capaz de atravesarla y atacar el tumor del cerebro
     Cuando las células envejecen, mueren a través de un proceso normal llamado apoptosis. Este sistema de pesos y contrapesos, en el que las células que no funcionan, viejas, mueren para dejar espacio a las células más nuevas, está ausente en las células del cáncer. Debido a que las células de cáncer no mueren, muchas de las terapias (por ejemplo, los medicamentos para quimioterapia) tratan de inducir la muerte celular. El honokiol desencadena la apoptosis de las células malignas mediante la activación de múltiples vías involucradas en el metabolismo
     Otro proceso normal en las células es el desarrollo de vasos sanguíneos (angiogénesis). Después del nacimiento, no hay mucha necesidad de angiogénesis, excepto cuando usted se corta o somete a cirugía. En cualquier de estas situaciones, los nuevos vasos sanguíneos se forman de una manera muy ordenada; en la angiogénesis del cáncer, los vasos sanguíneos forman un patrón irregular. El honokiol interrumpe la angiogénesis anormal bloqueando varias de sus vías bioquímicas
     El honokiol controlar la actividad de ciertas proteínas del ciclo celular normal, tales como NF-kB y P53, para inhibir el desarrollo del cáncer
     Las células cancerosas pueden ser resistentes a la  quimioterapia y radioterapia tradicional. El honokiol es notablemente sinérgico; mejora los efectos de los tratamientos tradicionales contra el cáncer mediante la sensibilización de las células cancerosas a los efectos de la quimioterapia y la radioterapia.  

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How Does Honokiol Fight Cancer?

Honokiol is a polyphenolic compound extracted and purified from magnolia bark. Traditionally, it has been used in Chinese and Japanese medicine for the treatment of digestive problems, anxiety, and stroke.1 Animal studies show that honokiol is quite effective at targeting various cancer cell lines, and the plant compound uses various pathways to stop cancer in its tracks.

Cancer cells use numerous tactics to avoid detection by the body’s immune system. The following are some of the ways in which cancer cells thrive: (1) the process of cell death (apoptosis) is missing in cancer cells, which allows unregulated cell growth; (2) cancer stem cells self-renews and produces diverse progeny, which resists chemotherapy and radiation therapy; and (3) dysmorphic blood vessel formation (cancer angiogenesis), which allows cancer cells to spread (metastasis).

Honokiol has a wide range of applications that target the specific mechanisms cancer cells employ in order to grow and spread inside the body. Its anticancer properties include the following:

  • Few drugs cross the blood brain barrier (BBB). The BBB is a semi-permeable, highly selective membrane; it separates the specialized fluid in the brain from the circulatory system. Fortunately, honokiol is able to cross the BBB to attack brain tumors.2
  • As cells get old, they die via a normal process called apoptosis. This checks-and-balances system, in which old nonfunctioning cells die off to make space for newer cells, is absent in cancer cells. Because cancer cells do not die, many of the therapies (e.g., chemotherapy drugs) work to induce cell death. Honokiol triggers apoptosis by activating multiple pathways involved in cell cycle arrest.3-5
  • Another normal process in cells is the development of blood vessels. After birth, there isn’t much need for angiogenesis, except when you cut yourself or get surgery. In either situation, new blood vessels form in a very orderly fashion; in cancer angiogenesis, blood vessels form an irregular pattern. Honokiol is a nutrient that interrupts abnormal angiogenesis by targeting various signaling pathways.6-9
  • Honokiol regulates signaling pathways to control normal cell cycle proteins activity, such as NF-kB and P53, to inhibit cancer growth.10,11
  • Cancer cells can be resistant to traditional chemotherapy drugs and radiation therapy. Honokiol is remarkably synergistic; it enhances the effects of traditional cancer treatments by sensitizing cancer cells to the effects of chemotherapy and radiation therapies.12-14

For over 25 years, my work in nutritional genomics (the study of how food influences genes) shows how the nutrients in foods and pharmaceutical-grade supplements turn on or turn off cancer. Honokiol, an amazing plant compound, is nontoxic and targets cancer using various pathways. I have been using honokiol for years to treat cancer. I also use honokiol to prevent cancer from becoming active. What many people don’t realize is that they are walking around with dormant cancer (based on autopsies of people who died in accidents or wars, dormant cancer has been found in various organs, such as the lungs and breasts). As part of the cancer-fighting therapy at GIO, I give my patients 200 mg of honokiol a day.

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References

1.         Ishitsuka K, Hideshima T, Hamasaki M, et al. Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and -independent apoptosis. Blood. September 1, 2005 2005;106(5):1794-1800.

2.         Wang X, Duan X, Yang G, et al. Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. PloS one. 2011;6(4):e18490.

3.         Xu H, Tang W, Du G, Kokudo N. Targeting apoptosis pathways in cancer with magnolol and honokiol, bioactive constituents of the bark of Magnolia officinalis. Drug discoveries & therapeutics. 2011;5(5).

4.         Arora S, Bhardwaj A, Srivastava SK, et al. Honokiol arrests cell cycle, induces apoptosis, and potentiates the cytotoxic effect of gemcitabine in human pancreatic cancer cells. PloS one. 2011;6(6):e21573.

5.         Kaushik G, Ramalingam S, Subramaniam D, et al. Honokiol induces cytotoxic and cytostatic effects in malignant melanoma cancer cells. The American Journal of Surgery. 2012;204(6):868-873.

6.         Ahn KS, Sethi G, Shishodia S, Sung B, Arbiser JL, Aggarwal BB. Honokiol potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through modulation of nuclear factor-kappaB activation pathway. Molecular cancer research : MCR. Sep 2006;4(9):621-633.

7.         Wen J, Fu A-f, Chen LJ, et al. Liposomal honokiol inhibits VEGF‐D‐induced lymphangiogenesis and metastasis in xenograft tumor model. International journal of cancer. 2009;124(11):2709-2718.

8.         Liu SH, Wang KB, Lan KH, et al. Calpain/SHP-1 interaction by honokiol dampening peritoneal dissemination of gastric cancer in nu/nu mice. PloS one. 2012;7(8):e43711.

9.         Steinmann P, Walters DK, Arlt MJ, et al. Antimetastatic activity of honokiol in osteosarcoma. Cancer. 2012;118(8):2117-2127.

10.      Fried LE, Arbiser JL. Honokiol, a multifunctional antiangiogenic and antitumor agent. Antioxidants & redox signaling. 2009;11(5):1139-1148.

11.      Dikalov S, Losik T, Arbiser JL. Honokiol is a potent scavenger of superoxide and peroxyl radicals. Biochemical pharmacology. 2008;76(5):589-596.

12.      Cheng N, Xia T, Han Y, He QJ, Zhao R, Ma JR. Synergistic antitumor effects of liposomal honokiol combined with cisplatin in colon cancer models. Oncology letters. 2011;2(5):957.

13.      Ponnurangam S, Mammen JM, Ramalingam S, et al. Honokiol in combination with radiation targets notch signaling to inhibit colon cancer stem cells. Molecular cancer therapeutics. 2012;11(4):963-972.

14.      He Z, Subramaniam D, Ramalingam S, et al. Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2011;301(5):G929.

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Structure and chemical characteristics of magnolol and honokiol. Magnolol (A) and honokiol (B) are isomers extracted from Magnolia officinalis. Both of magnolol and honokiol are lipophilic, biphenoid structure with molecular weight of 226.334. The melting point of magnolol is higher than that of honokiol.

Ho and Hong Journal of Biomedical Science 2012 19:70   doi:10.1186/1423-0127-19-70

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Part 1 of 5 from "Nutrition, Environment and Cancer - What You Need to Know," a talk by Mitchell L. Gaynor, M.D., well-known oncology specialist. Filmed in Wilson, Wyoming on February 18, 2014.

 

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 Como un oncólogo integrativo, creo que el tratamiento de los síntomas es necesario. Este enfoque, sin embargo, simplemente rasca la superficie. Los síntomas son, de hecho, las pistas a una causa subyacente de la enfermedad. Busco la causa fundamental de las enfermedades, y aplico tratamientos personalizados. En mi práctica, utilizo tratamientos médicos como la quimioterapia y la radioterapia para el tratamiento de pacientes con cáncer. También determino y manejo las deficiencias nutricionales en todos mis pacientes. A menudo administro glutatión IV debido a que una deficiencia de este antioxidante natural se ha relacionado con un mayor riesgo de desarrollar cáncer de mama, entre otros problemas de salud. Varios nutrientes previenen y tratan innumerables condiciones médicas . Algunos nutrientes han demostrado mejorar la eficacia o reducir los efectos adversos de otras drogas. He conocido y utilizado un compuesto vegetal que hace todas estas cosas, el honokiol.

 

 

How Does Honokiol Fight Cancer? - Gaynor Integrative ...

gaynoroncology.com/dramatic-anticancer-activity/

28/3/2014

 

 

 

 

 As an integrative oncologist, I believe that treating symptoms is necessary. This approach, however, simply scratches the surface. Symptoms are, in fact, clues to an underlying cause of disease. I find the root cause of diseases, and target the problems with personalized treatments. In my practice, I use medical treatments such as chemotherapy and radiation therapy to treat patients with cancer. I also test for and manage nutritional deficiencies in all my patients. I often administer IV glutathione because a deficiency of this natural antioxidant has been linked to a higher risk of developing breast cancer, among other health problems. Various nutrients prevent and treat myriad medical conditions. Some nutrients have been shown to enhance the efficacy or reduce the adverse effects of other drugs.  I have known about and used a plant compound that does all of these things—honokiol.

 

http://gaynoroncology.com/news/

 

 

http://healthremedies.com/_uploaded_files/magnolia-extract-honokiol-magnolol-90-120c-by-apromo_pic.jpghttp://healthremedies.com/_uploaded_files/magnolia-extract-honokiol-magnolol-90-120c-by-apromo_pic.jpg

 

HONOKIOL ANTITUMOROGENIC ACTIVITIES

Honokiol has shown pro-apoptotic effects in glioblastome multiforme cells [12] melanoma, sarcoma, myeloma, leukemia, bladder, lung, prostate, oral squamous cell carcinoma,[11]  and colon cancer cell lines.[13][14][15][16] Honokiol inhibits phosphorylation of Akt, p44/42 mitogen-activated protein kinase (MAPK), and src. Additionally, honokiol regulates the nuclear factor kappa B (NF-κB) activation pathway, an upstream effector of vascular endothelial growth factor (VEGF), MCL1, and cyclooxygenase 2 (COX-2), all significant pro-angiogenic and survival factors. Honokiol induces caspase-dependent apoptosis in a TRAIL-mediated manner, and potentiates the pro-apoptotic effects of doxorubicin and other etoposides. So potent is honokiol's pro-apoptotic effects that it overcomes even notoriously drug resistant neoplasms such as multiple myeloma and chronic B-cell leukemia. Honokiol also acts on the PI3K/mTOR pathway in tumor cells while maintaining pathway activity in T cells.[17]

http://en.wikipedia.org/wiki/Honokiol

 

 

El Gliosarcoma es uno de los tumores cerebrales malignos más comunes, y un enfoque prometedor para el tratamiento de gliosarcoma es el anti-angiogénesis, el enfoque que busca inhibir la formación de capilares sanguineos que alimentan el tumor. Sin embargo, la quimioterapia es obstruida por el obstáculo físico formado por la barrera hematoencefálica (BBB blood-brain barrier) y por la barrera entre la sangre y el fluido cerebroespinal (BCSFB blood-cerebrospinal fluid barrier). El Honokiol, un compuesto polifenólico extraído y purificado a partir de corteza de magnolia, ha sido conocido por poseer potents actividad en las enfermedades del sistema nervioso central, y propiedades anti-angiogénicas y anti-tumorales. Aquí, postulamos que el honokiol podría cruzar estas dos barreras y servir en el tratamiento del gliosarcoma.

 

Honokiol crosses BBB and BCSFB, and inhibits brain tumor ...

www.ncbi.nlm.nih.gov/pubmed/21559510

de X Wang - ‎2011 -

 

 

 

Honokiol crosses BBB and BCSFB, and inhibits brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model.

Abstract

BACKGROUND:

Gliosarcoma is one of the most common malignant brain tumors, and anti-angiogenesis is a promising approach for the treatment of gliosarcoma. However, chemotherapy is obstructed by the physical obstacle formed by the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB). Honokiol has been known to possess potent activities in the central nervous system diseases, and anti-angiogenic and anti-tumor properties. Here, we hypothesized that honokiol could cross the BBB and BCSFB for the treatment of gliosarcoma.

METHODOLOGIES:

We first evaluated the abilities of honokiol to cross the BBB and BCSFB by measuring the penetration of honokiol into brain and blood-cerebrospinal fluid, and compared the honokiol amount taken up by brain with that by other tissues. Then we investigated the effect of honokiol on the growth inhibition of rat 9L gliosarcoma cells and human U251 glioma cells in vitro. Finally we established rat 9L intracerebral gliosarcoma model in Fisher 344 rats and human U251 xenograft glioma model in nude mice to investigate the anti-tumor activity.

PRINCIPAL FINDINGS:

We showed for the first time that honokiol could effectively cross BBB and BCSFB. The ratios of brain/plasma concentration were respectively 1.29, 2.54, 2.56 and 2.72 at 5, 30, 60 and 120 min. And about 10% of honokiol in plasma crossed BCSFB into cerebrospinal fluid (CSF). In vitro, honokiol produced dose-dependent inhibition of the growth of rat 9L gliosarcoma cells and human U251 glioma cells with IC(50) of 15.61 µg/mL and 16.38 µg/mL, respectively. In vivo, treatment with 20 mg/kg body weight of honokiol (honokiol was given twice per week for 3 weeks by intravenous injection) resulted in significant reduction of tumor volume (112.70±10.16 mm(3)) compared with vehicle group (238.63±19.69 mm(3), P = 0.000), with 52.77% inhibiting rate in rat 9L intracerebral gliosarcoma model, and (1450.83±348.36 mm(3)) compared with vehicle group (2914.17±780.52 mm(3), P = 0.002), with 50.21% inhibiting rate in human U251 xenograft glioma model. Honokiol also significantly improved the survival over vehicle group in the two models (P<0.05).

CONCLUSIONS/SIGNIFICANCE:

This study provided the first evidence that honokiol could effectively cross BBB and BCSFB and inhibit brain tumor growth in rat 9L intracerebral gliosarcoma model and human U251 xenograft glioma model. It suggested a significant strategy for offering a potential new therapy for the treatment of gliosarcoma.

 

Honokiol, a Multifunctional Antiangiogenic and Antitumor ...

www.ncbi.nlm.nih.gov › ... › Antioxid Redox Signal 

de LE Fried - ‎2009 -

 

Cáncer cerebral: protooncogenes inhibidos por “transgén Omomyc” // Vall d´Hebron Institute of Oncology

* Malcolm Allison H  2014

 

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  • : Ecología y sostenibilidad socioambiental, énfasis en conservación de ríos y ecosistemas, denuncia de impacto de megaproyectos. Todo esto es indesligable de la política y por ello esta también se observa. Ecology, social and environmental sustainability, emphasis on conservation of rivers and ecosystems, denounces impact of megaprojects. All this is inseparable from politics, for it, the politics is also evaluated.
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  • Malcolm Allison H malcolm.mallison@gmail.com
  • Biólogo desde hace más de treinta años, desde la época en que aún los biólogos no eran empleados de los abogados ambientalistas. Actualmente preocupado …alarmado en realidad, por el LESIVO TRATADO DE(DES)INTEGRACIÓN ENERGÉTICA CON BRASIL
  • Biólogo desde hace más de treinta años, desde la época en que aún los biólogos no eran empleados de los abogados ambientalistas. Actualmente preocupado …alarmado en realidad, por el LESIVO TRATADO DE(DES)INTEGRACIÓN ENERGÉTICA CON BRASIL

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