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Article: Enhancing Tetrandrine Cytotoxicity In Human Lung Carcinoma A549 Cells By Suppressing Mitochondrial Atp Production

TitleEnhancing Tetrandrine Cytotoxicity In Human Lung Carcinoma A549 Cells By Suppressing Mitochondrial Atp Production
Authors
KeywordsTetrandrine
Mitochondria
ATP depletion
A549
Glycolysis
Issue Date2019
PublisherSpringer for German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and Sphingolipid Club. The Journal's web site is located at http://www.springer.com/biomed/pharmacology+%26+toxicology/journal/210
Citation
Naunyn-Schmiedeberg's Archives of Pharmacology, 2019, v. 392 n. 4, p. 427-436 How to Cite?
AbstractATP depletion induced by inhibiting glycolysis or mitochondrial ATP production has been demonstrated to cause cancer cell death. Whether ATP depletion can enhance the efficacy and potency of anti-cancer effects of herbal compounds is so far unknown. We examined the enhancing effect of ATP depletion on anti-cancer actions of tetrandrine (TET) in human lung carcinoma A549 cells. A 24-h incubation of A549 cells with tetrandrine caused a concentration-dependent cytotoxic effect (LC50 = 66.1 μM). Co-incubation with 20 mM 2-deoxyglucose (2-DG, glycolysis inhibitor) caused only a very slight enhancement of tetrandrine cytotoxicity. By contrast, inhibiting mitochondrial ATP production with oligomycin (10 μM, ATP synthase inhibitor) and FCCP (30 μM, uncoupling agent) (thus, oligo-FCCP) on its own caused only slight cell cytotoxicity but strongly potentiated tetrandrine cytotoxicity (tetrandrine LC50 = 15.6 μM). The stronger enhancing effect of oligo-FCCP than 2-DG on TET toxicity did not result from more severe overall ATP depletion, since both treatments caused a similar ATP level suppression. Neither oligo-FCCP nor 2-DG synergized with tetrandrine in decreasing mitochondrial membrane potential. TET on its own triggered reactive oxygen species (ROS) production, and oligo-FCCP, but not 2-DG, potentiated TET in causing ROS production. Taken together, our results suggest that inhibiting ATP production from mitochondria, but not from glycolysis, appears to be a very effective means in augmenting TET-triggered ROS production and hence toxicity in A549 cells.
Persistent Identifierhttp://hdl.handle.net/10722/279447
ISSN
2020 Impact Factor: 3.0
2015 SCImago Journal Rankings: 0.859
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChow, LWC-
dc.contributor.authorCheng, KS-
dc.contributor.authorLeong, F-
dc.contributor.authorCheung, CW-
dc.contributor.authorShiao, LR-
dc.contributor.authorLeung, YM-
dc.contributor.authorWong, KL-
dc.date.accessioned2019-11-01T07:17:32Z-
dc.date.available2019-11-01T07:17:32Z-
dc.date.issued2019-
dc.identifier.citationNaunyn-Schmiedeberg's Archives of Pharmacology, 2019, v. 392 n. 4, p. 427-436-
dc.identifier.issn0028-1298-
dc.identifier.urihttp://hdl.handle.net/10722/279447-
dc.description.abstractATP depletion induced by inhibiting glycolysis or mitochondrial ATP production has been demonstrated to cause cancer cell death. Whether ATP depletion can enhance the efficacy and potency of anti-cancer effects of herbal compounds is so far unknown. We examined the enhancing effect of ATP depletion on anti-cancer actions of tetrandrine (TET) in human lung carcinoma A549 cells. A 24-h incubation of A549 cells with tetrandrine caused a concentration-dependent cytotoxic effect (LC50 = 66.1 μM). Co-incubation with 20 mM 2-deoxyglucose (2-DG, glycolysis inhibitor) caused only a very slight enhancement of tetrandrine cytotoxicity. By contrast, inhibiting mitochondrial ATP production with oligomycin (10 μM, ATP synthase inhibitor) and FCCP (30 μM, uncoupling agent) (thus, oligo-FCCP) on its own caused only slight cell cytotoxicity but strongly potentiated tetrandrine cytotoxicity (tetrandrine LC50 = 15.6 μM). The stronger enhancing effect of oligo-FCCP than 2-DG on TET toxicity did not result from more severe overall ATP depletion, since both treatments caused a similar ATP level suppression. Neither oligo-FCCP nor 2-DG synergized with tetrandrine in decreasing mitochondrial membrane potential. TET on its own triggered reactive oxygen species (ROS) production, and oligo-FCCP, but not 2-DG, potentiated TET in causing ROS production. Taken together, our results suggest that inhibiting ATP production from mitochondria, but not from glycolysis, appears to be a very effective means in augmenting TET-triggered ROS production and hence toxicity in A549 cells.-
dc.languageeng-
dc.publisherSpringer for German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and Sphingolipid Club. The Journal's web site is located at http://www.springer.com/biomed/pharmacology+%26+toxicology/journal/210-
dc.relation.ispartofNaunyn-Schmiedeberg's Archives of Pharmacology-
dc.subjectTetrandrine-
dc.subjectMitochondria-
dc.subjectATP depletion-
dc.subjectA549-
dc.subjectGlycolysis-
dc.titleEnhancing Tetrandrine Cytotoxicity In Human Lung Carcinoma A549 Cells By Suppressing Mitochondrial Atp Production-
dc.typeArticle-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.emailWong, KL: wongeric@hku.hk-
dc.identifier.authorityCheung, CW=rp00244-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00210-018-01601-2-
dc.identifier.pmid30547225-
dc.identifier.scopuseid_2-s2.0-85058490787-
dc.identifier.hkuros308625-
dc.identifier.volume392-
dc.identifier.issue4-
dc.identifier.spage427-
dc.identifier.epage436-
dc.identifier.isiWOS:000461201900004-
dc.publisher.placeGermany-
dc.identifier.issnl0028-1298-

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