Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis in HepG2 cells

Paramasivan Poornima, Robin Sheeba Quency, Viswandha Vijaya Padma*

*Corresponding author for this work

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Evidence has accumulated concerning the medicinal application of Nelumbo nucifera in the treatment of various diseases. Neferine, an alkaloid from N. nucifera was found to exert cytotoxicity on liver cancer cells HepG2 in a dose-dependent manner. We evaluated its anticancer potential by studying its effect on mitochondrial membrane potential, intracellular calcium levels [Ca2+]i, cell membrane integrity, apoptotic body formation and DNA fragmentation in cultured HepG2 cells. The reactive oxygen species level has been increased upon neferine treatment with concomitant decrease in reduced glutathione. Our data further indicate reduction of ΔψM and increased [Ca2+]i during apoptosis induction by neferine with increased expression of apoptotic proteins such as Bax, Bad, cleaved forms of caspase 3, caspase 9 and PARP, with the downregulation of anti-apoptotic protein Bcl2 in HepG2 cells. Moreover, the expressions of tumour suppressor proteins p53 and PTEN were upregulated along with the downregulation of P-Akt. In addition, expression levels of TNF-α, p38 and ERK1/2 MAP kinases were increased upon neferine treatment. These results imply that mitochondrial- mediated ROS generation induced by neferine leads to caspase-dependent apoptosis in HepG2 cells.

Original languageEnglish
Pages (from-to)659-667
Number of pages9
JournalFood Chemistry
Volume136
Issue number2
Early online date4 Aug 2012
DOIs
Publication statusPublished - 15 Jan 2013
Externally publishedYes

Fingerprint

neferine
Hep G2 Cells
Nelumbo nucifera
reactive oxygen species
Reactive Oxygen Species
apoptosis
Apoptosis
calcium
Nelumbo
caspase-9
liver neoplasms
caspases
DNA fragmentation
cells
caspase-3
mitogen-activated protein kinase
membrane potential
Down-Regulation
cultured cells
hepatocytes

Cite this

Poornima, Paramasivan ; Quency, Robin Sheeba ; Padma, Viswandha Vijaya. / Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis in HepG2 cells. In: Food Chemistry. 2013 ; Vol. 136, No. 2. pp. 659-667.
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Neferine induces reactive oxygen species mediated intrinsic pathway of apoptosis in HepG2 cells. / Poornima, Paramasivan; Quency, Robin Sheeba; Padma, Viswandha Vijaya.

In: Food Chemistry, Vol. 136, No. 2, 15.01.2013, p. 659-667.

Research output: Contribution to journalArticle

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AU - Quency, Robin Sheeba

AU - Padma, Viswandha Vijaya

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AB - Evidence has accumulated concerning the medicinal application of Nelumbo nucifera in the treatment of various diseases. Neferine, an alkaloid from N. nucifera was found to exert cytotoxicity on liver cancer cells HepG2 in a dose-dependent manner. We evaluated its anticancer potential by studying its effect on mitochondrial membrane potential, intracellular calcium levels [Ca2+]i, cell membrane integrity, apoptotic body formation and DNA fragmentation in cultured HepG2 cells. The reactive oxygen species level has been increased upon neferine treatment with concomitant decrease in reduced glutathione. Our data further indicate reduction of ΔψM and increased [Ca2+]i during apoptosis induction by neferine with increased expression of apoptotic proteins such as Bax, Bad, cleaved forms of caspase 3, caspase 9 and PARP, with the downregulation of anti-apoptotic protein Bcl2 in HepG2 cells. Moreover, the expressions of tumour suppressor proteins p53 and PTEN were upregulated along with the downregulation of P-Akt. In addition, expression levels of TNF-α, p38 and ERK1/2 MAP kinases were increased upon neferine treatment. These results imply that mitochondrial- mediated ROS generation induced by neferine leads to caspase-dependent apoptosis in HepG2 cells.

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