{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:18:33Z","timestamp":1789186713043,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,4,18]],"date-time":"2017-04-18T00:00:00Z","timestamp":1492473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Science Centre in Poland","award":["UMO-2012\/05\/N\/NZ7\/00767"],"award-info":[{"award-number":["UMO-2012\/05\/N\/NZ7\/00767"]}]},{"name":"National Science Centre in Poland","award":["NN401031538"],"award-info":[{"award-number":["NN401031538"]}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:label\/><jats:p>Verapamil, an L\u2010type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of verapamil on autophagy and cell viability in greater detail. We report here that verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in <jats:styled-content style=\"fixed-case\">COLO<\/jats:styled-content> 205 cells, via treatment with the chloroquine (<jats:styled-content style=\"fixed-case\">CQ<\/jats:styled-content>) or by <jats:styled-content style=\"fixed-case\">CRISPR<\/jats:styled-content>\/Cas9\u2010mediated disruption of the autophagy genes <jats:italic>Atg7<\/jats:italic> and <jats:italic>Atg5<\/jats:italic>, causes an upregulation of apoptotic markers in response to verapamil. In search of a mechanism for this effect and because autophagy can often mitigate metabolic stress, we examined the impact of verapamil on cellular metabolism. This revealed that in normal prostate cells, verapamil diminishes glucose and glycolytic intermediate levels leading to adenosine 5\u2032\u2010triphosphate (<jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>) depletion. In contrast, in <jats:styled-content style=\"fixed-case\">COLO<\/jats:styled-content> 205 cells it enhances aerobic glycolysis and maintains <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>. Importantly, we found that the autophagic response in these cells is related to the activity of <jats:sc>l<\/jats:sc>\u2010lactate dehydrogenase A (<jats:styled-content style=\"fixed-case\">LDHA<\/jats:styled-content>, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chem.qmul.ac.uk\/iubmb\/enzyme\/EC1\/1\/1\/27.html\">EC 1.1.1.27<\/jats:ext-link>), as inhibition of <jats:styled-content style=\"fixed-case\">LDHA<\/jats:styled-content> reduces both basal and verapamil\u2010induced autophagy and consequently decreases cell viability. In summary, these findings not only identify a novel mechanism of cytoprotective autophagy induction but they also highlight the potential of using verapamil together with inhibitors of autophagy for the treatment of malignant disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Enzymes<\/jats:title><jats:p><jats:sc>l<\/jats:sc>\u2010lactate dehydrogenase (LDHA, <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chem.qmul.ac.uk\/iubmb\/enzyme\/EC1\/1\/1\/27.html\">EC 1.1.1.27<\/jats:ext-link>).<\/jats:p><\/jats:sec>","DOI":"10.1111\/febs.14064","type":"journal-article","created":{"date-parts":[[2017,3,25]],"date-time":"2017-03-25T14:22:59Z","timestamp":1490451779000},"page":"1370-1387","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Verapamil treatment induces cytoprotective autophagy by modulating cellular 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