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<p style="LINE-HEIGHT: 1.5em; MARGIN: 0.4em 0px 0.5em"><strong>Warburg's hypothesis</strong><span class="Apple-converted-space">&nbsp;</span>was postulated by the Nobel laureate<span class="Apple-converted-space">&nbsp;</span><a stylefont color="BACKGROUND-IMAGE: none; COLOR: rgb(90,54,150); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title=#5a3696">Otto Heinrich Warburg" href="http:<//biopedia.org/wiki/Otto_Heinrich_Warburg"><font color="#5a3696">Otto Heinrich Warburg</font></afont><span class="Apple-converted-space">&nbsp;</span>in 1924.<sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-0" class="reference"><a stylefont color="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http:#002bb8"><span>[</span>1<span>]</biopedia.orgspan></FCKeditorfont></editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-0"sup><font colorspan class="#002bb8Apple-converted-space"><span>[&nbsp;</span>1He hypothesized that<spanclass="Apple-converted-space">]&nbsp;</span></fontcolor="#002bb8">cancer</a></supfont>, malignant growth, and<span class="Apple-converted-space">&nbsp;</span>He hypothesized that<font color="#002bb8">tumor</font><span class="Apple-converted-space">&nbsp;</span>growth are caused by the fact that tumor cells mainly generate<a stylespan class="BACKGROUNDApple-IMAGE: none; COLOR: rgb(0,43,184)converted-space">&nbsp; TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Cancer" href="http:<//biopedia.org/wiki/Cancer"span><font color="#002bb8">cancerenergy</font><span class="Apple-converted-space">&nbsp;</aspan>, malignant growth, and(as e.g.<span class="Apple-converted-space">&nbsp;</span><a stylefont color="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial#002bb8" title="Tumor" href="http:>adenosine triphosphate<//biopedia.org/wiki/Tumor"><font color="#002bb8">tumor</font></afont><span class="Apple-converted-space">&nbsp;</span>growth are caused / ATP) by the fact that tumor cells mainly generatenon-oxidative breakdown of<span class="Apple-converted-space">&nbsp;</span><a stylefont color="#002bb8">glucose</font><span class="BACKGROUNDApple-IMAGE: noneconverted-space">&nbsp; COLOR: rgb</span>(0,43,184); TEXT-DECORATION: none; a process called<span class="Apple-webkitconverted-background-clip: initialspace">&nbsp; -webkit-background-origin: initial" title="Energy" href="http:<//biopedia.org/wiki/Energy"span><font color="#002bb8">energyglycolysis</font></a><span class="Apple-converted-space">). This is in contrast to &quot;healthy&nbspquot;</span>(as e.gcells which mainly generate energy from oxidative breakdown of pyruvate.Pyruvate is an end-product of<span class="Apple-converted-space">&nbsp;</span><a stylefont color="BACKGROUND-IMAGE: none; COLOR: rgb(0#002bb8">glycolysis</font>,43,184); TEXTand is<span class="Apple-DECORATION: none; converted-webkit-background-clip: initialspace">&nbsp; -webkit-background-origin: initial" title</span><font color="Adenosine triphosphate" href="http://biopedia.org/wiki/Adenosine_triphosphate"><font color="##002bb8">adenosine triphosphateoxidized</font></a><span class="Apple-converted-space">&nbsp;</span>/ ATP) by non-oxidative breakdown ofwithin the<span class="Apple-converted-space">&nbsp;</span><font color="#002bb8">mitochondria</font>. Hence, according to Warburg, cancer should be interpreted as a style<span class="BACKGROUNDApple-IMAGE: noneconverted-space">&nbsp; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Glucose" href="http:<//biopedia.org/wiki/Glucose"span><font color="#002bb8">glucosemitochondrial</font></a><span span class="Apple-converted-space">&nbsp;</span>(dysfunction. Warburg reported a process calledfundamental difference between normal and cancerous cells to be the ratio of glycolysis to respiration; this observation is also known as the<span class="Apple-converted-space">&nbsp;</span><a font color="#002bb8">Warburg effect</font>.</p><p style="BACKGROUNDLINE-IMAGEHEIGHT: none1.5em; COLORMARGIN: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Glycolysis" href="http://biopedia.org/wiki/Glycolysis.4em 0px 0.5em">It is now known that cancer is caused by<font colorspan class="Apple-converted-space">&nbsp;</span><font color="#002bb8">glycolysismutations</font></aspan class="Apple-converted-space">&nbsp;</span>). This is in contrast to &quot;healthy&quot; cells which mainly generate energy from oxidative breakdown of pyruvate. Pyruvate is an end-product ofthe<span class="Apple-converted-space">&nbsp;</span><a stylefont color="#002bb8">genome</font><span class="BACKGROUNDApple-IMAGE: none; COLOR: rgb(0,43,184); TEXTconverted-DECORATION: none; -webkit-background-clip: initialspace">&nbsp; </span>of the<span class="Apple-webkitconverted-background-origin: initialspace" title="Glycolysis" href="http:>&nbsp;<//biopedia.org/wiki/Glycolysis"span><font color="#002bb8">glycolysiscells</font><span class="Apple-converted-space">&nbsp;</span>in a>, and isprocess called<span class="Apple-converted-space">&nbsp;</span><a stylefont color="BACKGROUND-IMAGE: none; COLOR: rgb(0#002bb8">malignant transformation</font>,43,184); TEXTresulting in an uncontrolled growth of cells.<sup style="LINE-DECORATIONHEIGHT: none1em; FONT-webkit-background-clipSTYLE: initialnormal; FONT-webkit-background-originWEIGHT: initialnormal" classid="mwcite_ref-redirect1" titleclass="Oxidized" href="http://biopedia.org/wiki/Oxidizedreference"><font color="#002bb8">oxidized</fontspan>[</aspan>2<span class="Apple-converted-space">&nbsp;]</span>within the<span class="Apple-converted-space"/font>&nbsp;</spansup><a sup style="BACKGROUNDLINE-IMAGEHEIGHT: none1em; COLOR: rgb(0,43,184); TEXTFONT-DECORATIONSTYLE: nonenormal; FONT-webkit-background-clipWEIGHT: initial; -webkit-background-origin: initialnormal" classid="mwcite_ref-redirect2" titleclass="Mitochondria" href="http://biopedia.org/wiki/Mitochondriareference"><font color="#002bb8">mitochondria<span>[</fontspan>3<span>]</aspan></font></sup>. Hence, according to Warburg, cancer should be interpreted as a<span class="Apple-converted-space">&nbsp;</span>The metabolic differences observed by Warburg are now thought to be an adaption of cancer cells to the<a stylespan class="BACKGROUNDApple-IMAGE: none; COLOR: rgb(0,43,184); TEXTconverted-DECORATION: nonespace">&nbsp; -webkit-background-clip: initial; -webkit-background-origin: initial" class="mw-redirect" title="Mitochondrial" href="http://biopedia.org/wiki/Mitochondrial"><font color</span><font color="#002bb8">mitochondrialhypoxic</font></a><span class="Apple-converted-space">&nbsp;</span>dysfunction. Warburg reported a fundamental difference between normal (oxygen-deficient) conditions inside solid tumors, and cancerous cells to be therefore not the ratio cause, as he claimed, but an effect of glycolysis to respiration; this observation is also known as thecancer.</p><p style="LINE-HEIGHT: 1.5em; MARGIN: 0.4em 0px 0.5em">Warburg articulated his hypothesis in a paper entitled<span class="Apple-converted-space">&nbsp;</span><a styleem>The Prime Cause and Prevention of Cancer</em><span class="BACKGROUNDApple-IMAGE: none; COLOR: rgb(0,43,184); TEXTconverted-DECORATION: nonespace">&nbsp; </span>which he presented in lecture at the meeting of the Nobel-webkit-backgroundLaureates on June 30, 1966 at<span class="Apple-clip: initial; converted-webkit-background-origin: initialspace" title="Warburg effect" href="http:>&nbsp;<//biopedia.org/wiki/Warburg_effect"span><font color="#002bb8">Warburg effectLindau</font></a>, Lake Constance, Germany.In this speech, Warburg presented evidence in support of the claim that</p><p stylespan class="LINEApple-converted-HEIGHT: 1.5em; MARGIN: 0.4em 0px 0.5emspace">It is now known that cancer is caused by&nbsp;</span><font color="#002bb8">anaerobiosis</font><span class="Apple-converted-space">&nbsp;</span><was a style="BACKGROUND-IMAGE: none; COLOR: rgb(0primary cause of cancerous cells. Put in his own words,43,184)&quot; TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Mutation" href="http://biopediathe prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.org/wiki/Mutation">&quot;<font colorsup style="#002bb8LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-3" class="reference">mutations</fontcolor="#002bb8"></aspan>[</span class="Apple-converted-space">&nbsp;4</span>in the]</span class="Apple-converted-space">&nbsp;</spanfont><a /sup></p><p style="BACKGROUNDLINE-IMAGEHEIGHT: none1.5em; COLORMARGIN: rgb(0.4em 0px 0.5em">In recent years,43,184); TEXTWarburg's hypothesis has re-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Genome" href="http://biopedia.org/wiki/Genome">gained attention due to several discoveries linking impaired<font color="#002bb8">genomemitochondrial</font></a><span class="Apple-converted-space">&nbsp;</span>function as well as impaired respiration to the growth, division and expansion of thetumor cells. In a study by<span class="Apple-converted-space">&nbsp;</span><a stylefont color="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT#002bb8">Michael Ristow</font><span class="Apple-converted-DECORATION: nonespace">&nbsp; </span>and co-webkitworkers,<span class="Apple-backgroundconverted-clip: initialspace">&nbsp; -webkit-background-origin: initial" title="Cell (biology)" href="http:<//biopedia.org/wiki/Cell_(biology)"span><font color="#002bb8">cellscolon cancer</font></a><span class="Apple-converted-space">&nbsp;</span>in a process calledlines were modified to overexpress<span class="Apple-converted-space">&nbsp;</span><a stylefont color="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial#002bb8" title="Malignant transformation" href="http://biopedia.org/wiki/Malignant_transformation"><font color="#002bb8">malignant transformation>frataxin</font></a>, resulting in an uncontrolled growth of cells. The results of their work suggest that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals.<sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-14" class="reference"><a style="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http://biopedia.org/FCKeditor/editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-1"><font color="#002bb8"><span>[</span>2<span>]</span></font></a></sup><sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-2" class="reference"><a style="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http://biopedia.org/FCKeditor/editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-2"><font color="#002bb8"><span>[</span>3<span>]</span></font></a></sup><span class="Apple-converted-space">&nbsp;</span>The metabolic differences observed by Warburg are now thought to be an adaption of cancer cells to the<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Hypoxia (medical)" href="http://biopedia.org/wiki/Hypoxia_(medical)"><font color="#002bb8">hypoxic</font></a><span class="Apple-converted-space">&nbsp;</span>(oxygen-deficient) conditions inside solid tumors, and therefore not the cause, as he claimed, but an effect of cancer.</p><p style="LINE-HEIGHT: 1.5em; MARGIN: 0.4em 0px 0.5em">Warburg articulated his hypothesis in a paper entitled<span class="Apple-converted-space">&nbsp;</span><em>The Prime Cause and Prevention of Cancer</em><span class="Apple-converted-space">&nbsp;</span>which he presented in lecture at the meeting of the Nobel-Laureates on June 30, 1966 at<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Lindau" href="http://biopedia.org/wiki/Lindau"><font color="#002bb8">Lindau</font></a>, Lake Constance, Germany. In this speech, Warburg presented evidence in support of the claim that<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Fermentation (biochemistry)" href="http://biopedia.org/wiki/Fermentation_(biochemistry)"><font color="#002bb8">anaerobiosis</font></a><span class="Apple-converted-space">&nbsp;</span>was a primary cause of cancerous cells. Put in his own words, &quot;the prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar.&quot;<sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-3" class="reference"><a style="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http://biopedia.org/FCKeditor/editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-3"><font color="#002bb8"><span>[</span>4<span>]</span></font></a></sup></p><p style="LINE-HEIGHT: 1.5em; MARGIN: 0.4em 0px 0.5em">In recent years, Warburg's hypothesis has re-gained attention due to several discoveries linking impaired<a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" class="mw-redirect" title="Mitochondrial" href="http://biopedia.org/wiki/Mitochondrial"><font color="#002bb8">mitochondrial</font></a><span class="Apple-converted-space">&nbsp;</span>function as well as impaired respiration to the growth, division and expansion of tumor cells. In a study by<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Michael Ristow" href="http://biopedia.org/wiki/Michael_Ristow"><font color="#002bb8">Michael Ristow</font></a><span class="Apple-converted-space">&nbsp;</span>and co-workers,<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" class="mw-redirect" title="Colon cancer" href="http://biopedia.org/wiki/Colon_cancer"><font color="#002bb8">colon cancer</font></a><span class="Apple-converted-space">&nbsp;</span>lines were modified to overexpress<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Frataxin" href="http://biopedia.org/wiki/Frataxin"><font color="#002bb8">frataxin</font></a>. The results of their work suggest that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals.<sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-4" class="reference"><a style="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http://biopedia.org/FCKeditor/editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-4"><font color="#002bb8"><span>[</span>5<span>]</span></font></a></sup></p><p style="LINE-HEIGHT: 1.5em; MARGIN: 0.4em 0px 0.5em">Subsequent work has shown that the Warburg effect, indeed, might lead to a promising approach in the treatment of solid tumors. The drug<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Dichloroacetic acid" href="http://biopedia.org/wiki/Dichloroacetic_acid"><font color="#002bb8">dichloroacetic acid</font></a>, which promotes respiration and the activity of mitochondria, has been shown to kill cancer cells<span class="Apple-converted-space">&nbsp;</span><em>in vitro</em><span class="Apple-converted-space">&nbsp;</span>and in some animal models.<sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-bonnet2007_5-0" class="reference"><a style="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http://biopedia.org/FCKeditor/editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-bonnet2007-5"><font color="#002bb8"><span>[</span>6<span>]</span></font></a></sup><span class="Apple-converted-space">&nbsp;</span>The body often kills damaged cells by<span class="Apple-converted-space">&nbsp;</span><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Apoptosis" href="http://biopedia.org/wiki/Apoptosis"><font color="#002bb8">apoptosis</font></a>, a mechanism of self-destruction that involves mitochondria, but this mechanism fails in cancer cells where the mitochondria are shut down. According to one hypothesis, the reactivation of mitochondria in cancer cells might also restart their apoptosis program.<sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-6" class="reference"><a style="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http://biopedia.org/FCKeditor/editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-6"><font color="#002bb8"><span>[</span>7<span>]</span></font></a></sup><sup style="LINE-HEIGHT: 1em; FONT-STYLE: normal; FONT-WEIGHT: normal" id="cite_ref-7" class="reference"><a style="BACKGROUND-IMAGE: none; WHITE-SPACE: nowrap; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" href="http://biopedia.org/FCKeditor/editor/fckeditor.html?InstanceName=wpTextbox1&amp;Toolbar=Wiki#cite_note-7"><font color="#002bb8"><span>[</span>8<span>]</span></font></a></sup></p>

<h2 style="BACKGROUND-IMAGE: none; BORDER-BOTTOM: rgb(170,170,170) 1px solid; PADDING-BOTTOM: 0.17em; MARGIN: 0px 0px 0.6em; COLOR: black; FONT-SIZE: 19px; FONT-WEIGHT: normal; PADDING-TOP: 0.5em; -webkit-background-clip: initial; -webkit-background-origin: initial"><span style="FLOAT: right; MARGIN-LEFT: 5px; FONT-SIZE: 13px" class="editsection">[<a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Edit section: See also" href="http://biopedia.org/w/index.php?title=Warburg_hypothesis&amp;action=edit&amp;section=1"><font color="#002bb8">edit</font></a>]</span><span class="mw-headline">See also</span></h2>

<li style="MARGIN-BOTTOM: 0.1em"><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Carcinogen" href="http://biopedia.org/wiki/Carcinogen"><font color="#002bb8">Carcinogen</font></a></li> <li style="MARGIN-BOTTOM: 0.1em"><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="2-Deoxy-D-glucose" href="http://biopedia.org/wiki/2-Deoxy-D-glucose"><font color="#002bb8">2-Deoxy-D-glucose</font></a></li> <li style="MARGIN-BOTTOM: 0.1em"><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Ketogenic diet" href="http://biopedia.org/wiki/Ketogenic_diet"><font color="#002bb8">Ketogenic diet</font></a></li> <li style="MARGIN-BOTTOM: 0.1em"><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Pyruvic acid" href="http://biopedia.org/wiki/Pyruvic_acid"><font color="#002bb8">Pyruvic acid</font></a></li> <li style="MARGIN-BOTTOM: 0.1em"><a style="BACKGROUND-IMAGE: none; COLOR: rgb(0,43,184); TEXT-DECORATION: none; -webkit-background-clip: initial; -webkit-background-origin: initial" title="Respiration" href="http://biopedia.org/wiki/Respiration"><font color="#002bb8">Respiration</font></a></li>