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Enhancing tetrandrine cytotoxicity in human lung carcinoma A549 cells by suppressing mitochondrial ATP production.
Chow, Louis W C; Cheng, Ka-Shun; Leong, Fai; Cheung, Chi-Wai; Shiao, Lian-Ru; Leung, Yuk-Man; Wong, Kar-Lok.
Afiliação
  • Chow LWC; State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, China.
  • Cheng KS; UNIMED Medical Institute and Organisation for Oncology and Translational Research, Hong Kong, China.
  • Leong F; Organisation for Oncology and Translational Research, Hong Kong, China.
  • Cheung CW; Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
  • Shiao LR; Department of Anaesthesiology of Centro Hospitalar conde de Sao Januario, Macao Health Bureau, Macau, SAR, China.
  • Leung YM; Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • Wong KL; Department of Physiology, China Medical University, No.91, Hsueh-Shih Road, Taichung, 40402, Taiwan, Republic of China.
Naunyn Schmiedebergs Arch Pharmacol ; 392(4): 427-436, 2019 04.
Article em En | MEDLINE | ID: mdl-30547225
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trifosfato de Adenosina / Benzilisoquinolinas / Mitocôndrias / Antineoplásicos Fitogênicos Limite: Humans Idioma: En Revista: Naunyn Schmiedebergs Arch Pharmacol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Trifosfato de Adenosina / Benzilisoquinolinas / Mitocôndrias / Antineoplásicos Fitogênicos Limite: Humans Idioma: En Revista: Naunyn Schmiedebergs Arch Pharmacol Ano de publicação: 2019 Tipo de documento: Article País de afiliação: China