Neferine potentiates the antitumor effect of cisplatin in human lung adenocarcinoma cells via a mitochondria-mediated apoptosis pathway

Kalai Selvi Sivalingam, Poornima Paramasivan, Ching Feng Weng*, Vijaya padma Viswanadha

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes, as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome c, p53 levels, then activated cleavage forms of caspase-9, caspase-3, and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. J. Cell. Biochem. 118: 2865–2876, 2017.

Original languageEnglish
Pages (from-to)2865-2876
Number of pages12
JournalJournal of Cellular Biochemistry
Volume118
Issue number9
Early online date18 Feb 2017
DOIs
Publication statusPublished - 30 Sep 2017
Externally publishedYes

Fingerprint

neferine
Mitochondria
Cisplatin
Apoptosis
Cells
Matrix Metalloproteinases
Nelumbo
G1 Phase Cell Cycle Checkpoints
Adenocarcinoma of lung
Neoplasms
Chemotherapy
Caspase 9
Mitochondrial Membrane Potential

Cite this

@article{670591212db74251a401e346b9bed59e,
title = "Neferine potentiates the antitumor effect of cisplatin in human lung adenocarcinoma cells via a mitochondria-mediated apoptosis pathway",
abstract = "Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes, as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome c, p53 levels, then activated cleavage forms of caspase-9, caspase-3, and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. J. Cell. Biochem. 118: 2865–2876, 2017.",
author = "Sivalingam, {Kalai Selvi} and Poornima Paramasivan and Weng, {Ching Feng} and Viswanadha, {Vijaya padma}",
year = "2017",
month = "9",
day = "30",
doi = "10.1002/jcb.25937",
language = "English",
volume = "118",
pages = "2865--2876",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "9",

}

Neferine potentiates the antitumor effect of cisplatin in human lung adenocarcinoma cells via a mitochondria-mediated apoptosis pathway. / Sivalingam, Kalai Selvi; Paramasivan, Poornima; Weng, Ching Feng; Viswanadha, Vijaya padma.

In: Journal of Cellular Biochemistry, Vol. 118, No. 9, 30.09.2017, p. 2865-2876.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Neferine potentiates the antitumor effect of cisplatin in human lung adenocarcinoma cells via a mitochondria-mediated apoptosis pathway

AU - Sivalingam, Kalai Selvi

AU - Paramasivan, Poornima

AU - Weng, Ching Feng

AU - Viswanadha, Vijaya padma

PY - 2017/9/30

Y1 - 2017/9/30

N2 - Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes, as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome c, p53 levels, then activated cleavage forms of caspase-9, caspase-3, and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. J. Cell. Biochem. 118: 2865–2876, 2017.

AB - Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes, as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome c, p53 levels, then activated cleavage forms of caspase-9, caspase-3, and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. J. Cell. Biochem. 118: 2865–2876, 2017.

U2 - 10.1002/jcb.25937

DO - 10.1002/jcb.25937

M3 - Article

C2 - 28214344

AN - SCOPUS:85018379104

VL - 118

SP - 2865

EP - 2876

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 9

ER -