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Role of ErbB2 mediated AKT and MAPK pathway in gall bladder cell proliferation induced by argemone oil and butter yellow

Argemone oil and butter yellow induced gall bladder cell proliferation

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Abstract

The effect of noncytotoxic doses of argemone oil (AO) and butter yellow (BY), the common adulterants in edible oil, on free radical generation and signaling pathway for cell proliferation in primary cells of gall bladder (GB) was undertaken. AO and BY showed no cytotoxicity at 0.1 μl/ml and 0.1 μg/ml concentration, respectively. AO caused significant increase in ROS after 30 min and RNS after 24 h in GB cells while no change was observed following BY treatment. Enhanced level of COX-2 was observed following AO (0.1 μl/ml) and BY (0.1 μg/ml) treatment to cells for 24 h. AO treatment caused phosphorylation of ErbB2, AKT, ERK, and JNK along with increased thymidine uptake indicating cell proliferation ability in GB cells. BY treatment also showed significant expression of these proteins with the exception of phosphorylated JNK. These results suggest that AO and BY have cell proliferative potential in GB cells following up-regulation of COX-2 and ErbB2; however, their downstream signaling molecules and free radical generation have differential response, indicating that the mechanism of proliferation is different for both compounds and may have relevance in gall bladder cancer.

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Abbreviations

AO:

Argemone oil

BY:

Butter yellow

EMEM:

Eagle's minimum essential medium

MEM:

Minimum essential medium

HBSS:

Hank's balanced salt solution

FBS:

Fetal bovine serum

LDH:

Lactate dehydrogenase

MTT:

3-(4,5-dimethyl-2-yl)-2,5-dipehyl tetrazolium bromide

DMSO:

Dimethyl sulphoxide

PBS:

Phosphate buffer saline

ErbB2:

Neu proto oncogene

COX-2:

Cyclo oxigenase-2

AKT:

Serine threonine kinase

ERK:

Extracellular signal regulated kinase

JNK:

Jun-amino terminal kinase

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Acknowledgements

We are grateful to the Director of our Centre for his keen interest in the study. One of us (V M) is thankful to Council of Scientific and Industrial Research (CSIR)/University Grant Commission (UGC), New Delhi for the award of Senior Research Fellowship. Financial assistance of CSIR Supra Institutional Project (SIP-08) is gratefully acknowledged. The manuscript is IITR communication #2901.

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The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. Food Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Council of Scientific and Industrial Research, Post Box#80, Lucknow, 226 001, India

    Vivek Mishra, Kausar M. Ansari & Mukul Das

  2. Department of Biochemistry, University of Lucknow, Lucknow, India

    Vivek Mishra & Raj Khanna

Authors
  1. Vivek Mishra
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  2. Kausar M. Ansari
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  3. Raj Khanna
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  4. Mukul Das
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Correspondence to Mukul Das.

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Mishra, V., Ansari, K.M., Khanna, R. et al. Role of ErbB2 mediated AKT and MAPK pathway in gall bladder cell proliferation induced by argemone oil and butter yellow. Cell Biol Toxicol 28, 149–159 (2012). https://doi.org/10.1007/s10565-011-9207-5

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  • DOI: https://doi.org/10.1007/s10565-011-9207-5

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