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      Ayahuasca and cancer treatment

      research-article
      1 , 2 ,
      SAGE Open Medicine
      SAGE Publications
      Ayahuasca, N, N-dimethyltryptamine, harmine, cancer, sigma-1 receptor

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          Abstract

          Objectives:

          Comprehensively review the evidence regarding the use of ayahuasca, an Amerindian medicine traditionally used to treat many different illnesses and diseases, to treat some types of cancer.

          Methods:

          An in-depth review of the literature was conducted using PubMed, books, institutional magazines, conferences and online texts in nonprofessional sources regarding the biomedical knowledge about ayahuasca in general with a specific focus in its possible relations to the treatment of cancer.

          Results:

          At least nine case reports regarding the use of ayahuasca in the treatment of prostate, brain, ovarian, uterine, stomach, breast, and colon cancers were found. Several of these were considered improvements, one case was considered worse, and one case was rated as difficult to evaluate. A theoretical model is presented which explains these effects at the cellular, molecular, and psychosocial levels. Particular attention is given to ayahuasca’s pharmacological effects through the activity of N,N-dimethyltryptamine at intracellular sigma-1 receptors. The effects of other components of ayahuasca, such as harmine, tetrahydroharmine, and harmaline, are also considered.

          Conclusion:

          The proposed model, based on the molecular and cellular biology of ayahuasca’s known active components and the available clinical reports, suggests that these accounts may have consistent biological underpinnings. Further study of ayahuasca’s possible antitumor effects is important because cancer patients continue to seek out this traditional medicine. Consequently, based on the social and anthropological observations of the use of this brew, suggestions are provided for further research into the safety and efficacy of ayahuasca as a possible medicinal aid in the treatment of cancer.

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          Most cited references95

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          MAM: more than just a housekeeper.

          The physical association between the endoplasmic reticulum (ER) and mitochondria, which is known as the mitochondria-associated ER membrane (MAM), has important roles in various cellular 'housekeeping' functions including the non-vesicular transports of phospholipids. It has recently become clear that the MAM also enables highly efficient transmission of Ca(2+) from the ER to mitochondria to stimulate oxidative metabolism and, conversely, might enable the metabolically energized mitochondria to regulate the ER Ca(2+) homeostasis. Recent studies have shed light on molecular chaperones such as calnexin, calreticulin, ERp44, ERp57, grp75 and the sigma-1 receptor at the MAM, which regulate the association between the two organelles. The MAM thus integrates signal transduction with metabolic pathways to regulate the communication and functional interactions between the ER and mitochondrion.
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            Choosing between glycolysis and oxidative phosphorylation: a tumor's dilemma?

            A considerable amount of knowledge has been produced during the last five years on the bioenergetics of cancer cells, leading to a better understanding of the regulation of energy metabolism during oncogenesis, or in adverse conditions of energy substrate intermittent deprivation. The general enhancement of the glycolytic machinery in various cancer cell lines is well described and recent analyses give a better view of the changes in mitochondrial oxidative phosphorylation during oncogenesis. While some studies demonstrate a reduction of oxidative phosphorylation (OXPHOS) capacity in different types of cancer cells, other investigations revealed contradictory modifications with the upregulation of OXPHOS components and a larger dependency of cancer cells on oxidative energy substrates for anabolism and energy production. This apparent conflictual picture is explained by differences in tumor size, hypoxia, and the sequence of oncogenes activated. The role of p53, C-MYC, Oct and RAS on the control of mitochondrial respiration and glutamine utilization has been explained recently on artificial models of tumorigenesis. Likewise, the generation of induced pluripotent stem cells from oncogene activation also showed the role of C-MYC and Oct in the regulation of mitochondrial biogenesis and ROS generation. In this review article we put emphasis on the description of various bioenergetic types of tumors, from exclusively glycolytic to mainly OXPHOS, and the modulation of both the metabolic apparatus and the modalities of energy substrate utilization according to tumor stage, serial oncogene activation and associated or not fluctuating microenvironmental substrate conditions. We conclude on the importance of a dynamic view of tumor bioenergetics. Copyright © 2010 Elsevier B.V. All rights reserved.
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              The sigma-1 receptor chaperone as an inter-organelle signaling modulator.

              Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intramitochondrial calcium (Ca(2+)) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca(2+) homeostasis and ER-mitochondrion-plasma membrane signaling regulates hippocampal dendritic spine formation. Here, we propose that the sigma-1 receptor (Sig-1R), an ER chaperone protein, acts as an inter-organelle signaling modulator. Sig-1Rs normally reside at the ER-mitochondrion contact called the MAM (mitochondrion-associated ER membrane), where Sig-1Rs regulate ER-mitochondrion signaling and ER-nucleus crosstalk. When cells are stimulated by ligands or undergo prolonged stress, Sig-1Rs translocate from the MAM to the ER reticular network and plasmalemma/plasma membrane to regulate a variety of functional proteins, including ion channels, receptors and kinases. Thus, the Sig-1R serves as an inter-organelle signaling modulator locally at the MAM and remotely at the plasmalemma/plasma membrane. Many pharmacological/physiological effects of Sig-1Rs might relate to this unique action of Sig-1Rs. Published by Elsevier Ltd.
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                Author and article information

                Journal
                SAGE Open Med
                SAGE Open Med
                SMO
                spsmo
                SAGE Open Medicine
                SAGE Publications (Sage UK: London, England )
                2050-3121
                18 October 2013
                2013
                : 1
                : 2050312113508389
                Affiliations
                [1 ]Departamento de Psiquiatria, Universidade Federal de São Paulo, São Paulo, Brazil
                [2 ]Instituto Plantando Consciencia, São Paulo, Brazil
                Author notes
                [*]Eduardo E Schenberg, Rua Iraci 340, Jardim Paulistano, CEP 01457-000 São Paulo, SP, Brazil. Email: eduardoschenberg@ 123456gmail.com
                Article
                10.1177_2050312113508389
                10.1177/2050312113508389
                4687784
                5c0fd0ad-8dbd-438d-91a5-f708492fb138
                © The Author(s) 2013
                History
                Categories
                Original Article
                Custom metadata
                corrected-proof
                January - December 2013

                ayahuasca,n,n-dimethyltryptamine,harmine,cancer,sigma-1 receptor

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