Phosphotyrosine profiling of curcumin-induced signaling.
BACKGROUND
Curcumin, derived from the rhizome Curcuma longa, is a natural anti-cancer agent and has been shown to inhibit proliferation and survival of tumor cells. Although the anti-cancer effects of curcumin are well established, detailed understanding of the signaling pathways altered by curcumin is still lacking. In this study, we carried out SILAC-based quantitative proteomic analysis of a HNSCC cell line (CAL 27) to investigate tyrosine signaling in response to curcumin.


RESULTS
Using high resolution Orbitrap Fusion Tribrid Fourier transform mass spectrometer, we identified 627 phosphotyrosine sites mapping to 359 proteins. We observed alterations in the level of phosphorylation of 304 sites corresponding to 197 proteins upon curcumin treatment. We report here for the first time, curcumin-induced alterations in the phosphorylation of several kinases including TNK2, FRK, AXL, MAPK12 and phosphatases such as PTPN6, PTPRK, and INPPL1 among others. Pathway analysis revealed that the proteins differentially phosphorylated in response to curcumin are known to be involved in focal adhesion kinase signaling and actin cytoskeleton reorganization.


CONCLUSIONS
The study indicates that curcumin may regulate cellular processes such as proliferation and migration through perturbation of the focal adhesion kinase pathway. This is the first quantitative phosphoproteomics-based study demonstrating the signaling events that are altered in response to curcumin. Considering the importance of curcumin as an anti-cancer agent, this study will significantly improve the current knowledge of curcumin-mediated signaling in cancer.
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|Manipal University, Madhav Nagar, Manipal, 576104 India.
Gajanan
G
Sathe
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018 India.
Sneha M
SM
Pinto
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605014 India.
Nazia
N
Syed
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
Vishalakshi
V
Nanjappa
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|School of Biotechnology, KIIT University, Bhubaneswar, 751024 India.
Hitendra S
HS
Solanki
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
Santosh
S
Renuse
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|Manipal University, Madhav Nagar, Manipal, 576104 India.
Sandip
S
Chavan
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|School of Biotechnology, KIIT University, Bhubaneswar, 751024 India.
Aafaque Ahmad
AA
Khan
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|School of Biotechnology, KIIT University, Bhubaneswar, 751024 India.
Arun H
AH
Patil
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|Centre of Excellence in Bioinformatics, School of Life Sciences, Pondicherry University, Puducherry, 605014 India.
Raja Sekhar
RS
Nirujogi
Amrita School of Biotechnology, Amrita University, Kollam, 690525 India.
Bipin
B
Nair
School of Biotechnology, KIIT University, Bhubaneswar, 751024 India.
Premendu Prakash
PP
Mathur
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018 India.|NIMHANS-IOB Proteomics and Bioinformatics Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bangalore, 560029 India.
T S Keshava
TSK
Prasad
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018 India.
Harsha
H
Gowda
Institute of Bioinformatics, Unit I, 7th Floor, Discoverer Building, International Tech Park, Bangalore, 560066 India.|YU-IOB Center for Systems Biology and Molecular Medicine, Yenepoya University, Mangalore, 575018 India.
Aditi
0000-0002-6518-095X
A
Chatterjee
Curcumin; In vivo labeling; Oral cancer; Phosphoproteomics