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- Publisher Website: 10.1007/s00210-018-01601-2
- Scopus: eid_2-s2.0-85058490787
- PMID: 30547225
- WOS: WOS:000461201900004
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Article: Enhancing Tetrandrine Cytotoxicity In Human Lung Carcinoma A549 Cells By Suppressing Mitochondrial Atp Production
Title | Enhancing Tetrandrine Cytotoxicity In Human Lung Carcinoma A549 Cells By Suppressing Mitochondrial Atp Production |
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Authors | |
Keywords | Tetrandrine Mitochondria ATP depletion A549 Glycolysis |
Issue Date | 2019 |
Publisher | Springer 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? |
Abstract | ATP 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 Identifier | http://hdl.handle.net/10722/279447 |
ISSN | 2023 Impact Factor: 3.1 2023 SCImago Journal Rankings: 0.735 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Chow, LWC | - |
dc.contributor.author | Cheng, KS | - |
dc.contributor.author | Leong, F | - |
dc.contributor.author | Cheung, CW | - |
dc.contributor.author | Shiao, LR | - |
dc.contributor.author | Leung, YM | - |
dc.contributor.author | Wong, KL | - |
dc.date.accessioned | 2019-11-01T07:17:32Z | - |
dc.date.available | 2019-11-01T07:17:32Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Naunyn-Schmiedeberg's Archives of Pharmacology, 2019, v. 392 n. 4, p. 427-436 | - |
dc.identifier.issn | 0028-1298 | - |
dc.identifier.uri | http://hdl.handle.net/10722/279447 | - |
dc.description.abstract | ATP 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.language | eng | - |
dc.publisher | Springer 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.ispartof | Naunyn-Schmiedeberg's Archives of Pharmacology | - |
dc.subject | Tetrandrine | - |
dc.subject | Mitochondria | - |
dc.subject | ATP depletion | - |
dc.subject | A549 | - |
dc.subject | Glycolysis | - |
dc.title | Enhancing Tetrandrine Cytotoxicity In Human Lung Carcinoma A549 Cells By Suppressing Mitochondrial Atp Production | - |
dc.type | Article | - |
dc.identifier.email | Cheung, CW: cheucw@hku.hk | - |
dc.identifier.email | Wong, KL: wongeric@hku.hk | - |
dc.identifier.authority | Cheung, CW=rp00244 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1007/s00210-018-01601-2 | - |
dc.identifier.pmid | 30547225 | - |
dc.identifier.scopus | eid_2-s2.0-85058490787 | - |
dc.identifier.hkuros | 308625 | - |
dc.identifier.volume | 392 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 427 | - |
dc.identifier.epage | 436 | - |
dc.identifier.isi | WOS:000461201900004 | - |
dc.publisher.place | Germany | - |
dc.identifier.issnl | 0028-1298 | - |