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      A novel therapeutic anticancer property of raw garlic extract via injection but not ingestion

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      1 , 2 , 1 , 3 , 1 , 3 ,
      Cell Death Discovery
      Nature Publishing Group UK

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          Abstract

          Prior studies suggest a possibility that the anticancer property of garlic is more effective only when exposed directly to cancer cells than absorbed first by the normal epithelial cells of the gastrointestinal tract wall. We tested this possibility in two mouse models of highly aggressive malignancies that cannot yet be cured by conventional therapies: sarcoma 180- and EL4-induced lethal ascites. Daily oral gavages of raw garlic extract (RGE; equivalent to 100 mg wet weight) for 21 days failed to offer any meaningful effect in the mice with malignancies. However, the daily injection of the same amounts of the same materials for 21 days completely cured all the mice of cancer. This novel anticancer activity of RGE was present entirely in the size fraction of the molecules smaller than 3000 Dalton rather than the larger molecules and was completely partitioned into the organic phase rather than into the aqueous phase. One half of the anticancer activity was inactivated by heating at 100 °C for 10 min, suggesting that multiple components were concertedly involved. In a direct comparison, the RGE was significantly more effective in killing the cultured cancer cells in vitro than the extracts from other 21 raw vegetables and fruits. In cell culture, RGE killed a wide variety of different cancer cells regardless of species of origin and cell types. Cancer cells generally are well known to be defective in many common metabolic pathways present in their normal cell counterpart for processing normal nutrients. The metabolism of these otherwise normal nutrients could be stalled in the cancer cells and become cytotoxic. The most-effective way of treating cancer by RGE may be the direct injection instead of eating the cooked garlic.

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          Cancer metabolism: the Warburg effect today.

          One of the first studies on the energy metabolism of a tumour was carried out, in 1922, in the laboratory of Otto Warburg. He established that cancer cells exhibited a specific metabolic pattern, characterized by a shift from respiration to fermentation, which has been later named the Warburg effect. Considerable work has been done since then, deepening our understanding of the process, with consequences for diagnosis and therapy. This review presents facts and perspectives on the Warburg effect for the 21st century. Copyright © 2010 Elsevier Inc. All rights reserved.
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            Molecular distinction of phosphatidylcholine synthesis between the CDP-choline pathway and phosphatidylethanolamine methylation pathway.

            In addition to the CDP-choline pathway for phosphatidylcholine (PC) synthesis, the liver has a unique phosphatidylethanolamine (PE) methyltransferase activity for PC synthesis via three methylations of the ethanolamine moiety of PE. Previous studies indicate that the two pathways are functionally different and not interchangeable even though PC is the common product of both pathways. This study was designed to test the hypothesis that these two pathways produce different profiles of PC species. The PC species from these two pathways were labeled with specific stable isotope precursors, D9-choline and D4-ethanolamine, and analyzed by electrospray tandem mass spectrometry. Our studies revealed a profound distinction in PC profiles between the CDP-choline pathway and the PE methylation pathway. PC molecules produced from the CDP-choline pathway were mainly comprised of medium chain, saturated (e.g. 16:0/18:0) species. On the other hand, PC molecules from the PE methylation pathway were much more diverse and were comprised of significantly more long chain, polyunsaturated (e.g. 18:0/20:4) species. PC species from the methylation pathway contained a higher percentage of arachidonate and were more diverse than those from the CDP-choline pathway. This profound distinction of PC profiles may contribute to the different functions of these two pathways in the liver.
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              Warburg effect(s)—a biographical sketch of Otto Warburg and his impacts on tumor metabolism

              Virtually everyone working in cancer research is familiar with the “Warburg effect”, i.e., anaerobic glycolysis in the presence of oxygen in tumor cells. However, few people nowadays are aware of what lead Otto Warburg to the discovery of this observation and how his other scientific contributions are seminal to our present knowledge of metabolic and energetic processes in cells. Since science is a human endeavor, and a scientist is imbedded in a network of social and academic contacts, it is worth taking a glimpse into the biography of Otto Warburg to illustrate some of these influences and the historical landmarks in his life. His creative and innovative thinking and his experimental virtuosity set the framework for his scientific achievements, which were pioneering not only for cancer research. Here, I shall allude to the prestigious family background in imperial Germany; his relationships to Einstein, Meyerhof, Krebs, and other Nobel and notable scientists; his innovative technical developments and their applications in the advancement of biomedical sciences, including the manometer, tissue slicing, and cell cultivation. The latter were experimental prerequisites for the first metabolic measurements with tumor cells in the 1920s. In the 1930s–1940s, he improved spectrophotometry for chemical analysis and developed the optical tests for measuring activities of glycolytic enzymes. Warburg’s reputation brought him invitations to the USA and contacts with the Rockefeller Foundation; he received the Nobel Prize in 1931. World politics and world wars heavily affected Warburg’s scientific survival in Berlin. But, after his second postwar recovery, Warburg’s drive for unraveling the energetic processes of life, both in plants and in tumor cells, continued until his death in 1970. The legacy of Otto Warburg is not only the Warburg effect, but also the identification of the “respiratory ferment” and hydrogen-transferring cofactors and the isolation of glycolytic enzymes. His hypothesis of respiratory damage being the cause of cancer remains to be a provocative scientific issue, along with its implications for cancer treatment and prevention. Warburg is therefore still stimulating our thinking, as documented in a soaring increase in publications citing his name in the context of tumor metabolism.
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                Author and article information

                Contributors
                +336-978-8014 , zhengcui@wakehealth.edu
                Journal
                Cell Death Discov
                Cell Death Discov
                Cell Death Discovery
                Nature Publishing Group UK (London )
                2058-7716
                21 November 2018
                21 November 2018
                2018
                : 4
                : 108
                Affiliations
                [1 ]ISNI 0000 0004 0459 1231, GRID grid.412860.9, Department of Pathology, , Wake Forest University Health Sciences, ; Winston-Salem, 27157 NC USA
                [2 ]ISNI 0000 0004 0368 7223, GRID grid.33199.31, Family Planning Research Institute, Center of Reproductive Medicine, Tongji College, , Huazhong University of Science and Technology, ; Wuhan430030, Hubei, China
                [3 ]ISNI 0000000123704535, GRID grid.24516.34, The Institute for Translational Nanomedicine, Shanghai East Hospital, , Tongji University School of Medicine, ; Shanghai, 200120 China
                Article
                122
                10.1038/s41420-018-0122-x
                6249268
                eb45f86b-b210-4d23-b8ec-903859071857
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 September 2018
                : 22 October 2018
                : 30 October 2018
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