Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells

Paramasivan Poornima, Velmurugan Bharath Kumar, Ching Feng Weng*, Viswanadha Vijaya Padma

*Corresponding author for this work

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 Ca2+ 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.

Original languageEnglish
Pages (from-to)87-98
Number of pages12
JournalFood and Chemical Toxicology
Volume68
Early online date13 Mar 2014
DOIs
Publication statusPublished - 30 Jun 2014
Externally publishedYes

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neferine
doxorubicin
Doxorubicin
apoptosis
lungs
Apoptosis
Lung
cells
antineoplastic agents
Cell death
Antineoplastic Agents
Toxicity
cell death
Cell Death
Cells
toxicity
A549 Cells
Oxidative stress
Lotus
Mitochondrial Membrane Potential

Cite this

Poornima, Paramasivan ; Kumar, Velmurugan Bharath ; Weng, Ching Feng ; Padma, Viswanadha Vijaya. / Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells. In: Food and Chemical Toxicology. 2014 ; Vol. 68. pp. 87-98.
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Doxorubicin induced apoptosis was potentiated by neferine in human lung adenocarcima, A549 cells. / Poornima, Paramasivan; Kumar, Velmurugan Bharath; Weng, Ching Feng; Padma, Viswanadha Vijaya.

In: Food and Chemical Toxicology, Vol. 68, 30.06.2014, p. 87-98.

Research output: Contribution to journalArticle

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