title: Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells.
abstract: Doxorubicin (DOX) is the best anticancer agent that has ever been used, but acquired tumor resistance and dose limiting toxicity are major road blocks. Concomitant use of natural compounds is a promising strategy to overcome this problem. Neferine, a proven anticancer agent is found in green embryos of lotus seed. The study demonstrates that neferine acts as an effective enhancer of DOX-induced cell death in A549 cells through ROS mediated apoptosis with MAPK activation and inhibition of NF-κB nuclear translocation. Cotreatment of cells with neferine significantly enhanced intracellular DOX-accumulation. Neferine and DOX in combination also triggered oxidative stress through intracellular Ca(2+) accumulation and dissipation of mitochondrial membrane potential in addition to significant loss of cellular antioxidant pool. The MAPK inhibitor effectively decreased the cell-death induced by neferine and DOX. Pretreatment of cells with glutathione reversed the apoptosis induced by combined regimen and recovered the Bcl2/Bax ratio. Moreover, neferine treatment significantly increased the cell viability of DOX-treated cardiomyocytes indicating a possible protective role of neferine towards DOX-induced cardiotoxicity. Taken together, our results suggest that a strategy of using neferine and DOX in combination could be helpful to increase the efficacy of DOX and to achieve anticancer synergism by curbing the toxicity.
authors.affiliation: Animal Tissue Culture and Molecular Genetics Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641046, Tamilnadu, India.
authors.forename: Paramasivan
authors.initials: P
authors.lastname: Poornima
authors.affiliation: Laboratory of Molecular Physiology, Institute of Biotechnology, Department of Life Sciences, National Dong Hwa University, Hualien 974, Taiwan.
authors.forename: Velmurugan Bharath
authors.initials: VB
authors.lastname: Kumar
authors.affiliation: Laboratory of Molecular Physiology, Institute of Biotechnology, Department of Life Sciences, National Dong Hwa University, Hualien 974, Taiwan. Electronic address: cfweng@mail.ndhu.edu.tw.
authors.forename: Ching Feng
authors.initials: CF
authors.lastname: Weng
authors.affiliation: Animal Tissue Culture and Molecular Genetics Laboratory, Department of Biotechnology, School of Biotechnology and Genetic Engineering, Bharathiar University, Coimbatore 641046, Tamilnadu, India. Electronic address: vvijayapadma@rediffmail.com.
authors.forename: Viswanadha Vijaya
authors.initials: VV
authors.lastname: Padma
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D044182:Benzylisoquinolines / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000903:Antibiotics, Antineoplastic; D044182:Benzylisoquinolines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C057222:neferine; D009569:Nitric Oxide; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D005978:Glutathione
keywords: Apoptosis; Doxorubicin; MAPK; NF-κB; Neferine; ROS