Program: Human resources
Type of the
project: Research projects for young research teams
This work was supported
by a grant of the Romanian
National
Authority for Scientific Research, CNCS – UEFISCDI
Title: Efects of polyphenols in modulating the
relationship between ErbB proteins and cell cycle
progression in breast and epidermoid adenocarcinoma
Project number: PN-II-RU-TE-2011-3-0204
Contract: 111/10.10.2011
Duration: 36 months
Begining of the project: 10.10.2011
End of the project: 10.09.2014
Summary
ErbB
proteins, members of the receptor tyrosine kinase (RTKs)
family, and their signaling pathways play pivotal roles
in migration, adhesion, apoptosis and proliferation of
cells. In cancer cells the expression, interactions and
signaling of ErbB proteins are often not subject to the
tight regulation observed under physiologic conditions.
Recent studies indicate that RTKs represent one of the
critical targets of polyphenols in diminishing cancer
cell proliferation. In the framework of our project we
plan to investigate the effects of polyphenols on cell
cycle progression and apoptosis in relation to the
expression levels, interactions, activation state and
signaling pathways of ErbB proteins in breast and
epidermoid carcinoma cell lines. We will correlate these
parameters with the types and concentrations of
polyphenols. For our experiments we will generally use
flow cytometry that provides robust statistical data.
ErbB protein interactions will be investigated by both
confocal microscopic immunofluorescent approaches
(co-localization) and flow cytometric fluorescence
resonance energy transfer. The activation state of ErbB
proteins and their signaling pathways (e.g. PI3K/Akt
kinase) will be investigated by western blotting. We
expect that the project will clarify the role of
polyphenols in influencing the ErbB receptor system and
it will contribute to establishing the role of
polyphenols in the treatment and chemoprevention of
cancer.
Key
words: ErbB proteins, polyphenols, tumor cells, cell
cycle, apoptosis
Specific objectives
- Studying the impact of the polyphenols on the cell cycle
progression, apoptosis and cell viability
- Investigating the effect of polyphenols on the expression
level of ErbB proteins
- Studying the effects of polyphenols on the association
state of ErbB proteins:
interactions between ErbB
proteins and β1-integrin or laminin
receptor (67LR), ErbB1 homoassociation, ErbB2 homoassociation
- Investigating the correlation between the
activation state of ErbB
proteins and polyphenol
treatments
- Investigating the effects of polyphenols on ErbB signalling pathways
Milestones
and tasks (.pdf)
Team:
Lecturer Dr. Mocanu Maria-Magdalena - principal investigator
Prof. Dr. Ganea Constanta - senior researcher
Assoc. Prof. Dr. Irina Baran - postdoctoral researcher
Laura Georgescu - student
Flavia Iacobescu - student
Rodica Zaharia - technical assistant
Elena Constantin - technical assistant
Scientific reports : .pdf (english)
Disemination
of the results:
Publications:
- Mocanu Maria-Magdalena, Surcel
Mihaela, Ursaciuc Cornel, Katona Eva, Ganea
Constanta, Antiproliferative effect of
quercetin in mammary and epidermoid cancer, ROMANIAN
BIOTECHNOLOGICAL LETTERS, 2013, vol. 18, no. 6, pp.
8796-8803, (IF. 0.363)(is 0.115) [ link
]
- M.M. Mocanu, C. Ganea, L.
Georgescu, T. Varadi, D. Shrestha, I. Baran, E. Katona, P.
Nagy, J. Szöllösi, Epigallocatechin-gallate determines
ErbB proteins downregulation, cell death mediated by
67kDa laminin receptor and altered lipid order in
mammary and epidermoid carcinoma cells, 2013,
J. NAT. PROD.,
DOI: 10.1021/np4007712
Publication Date (Web): January 23, 2014, (IF. 3.285) (is. 1.867) [ link ]
- Mocanu MM, Ganea C, Siposova K,
Filippi A, Demjen E, Marek J, Bednarikova Z, Antosova A,
Baran I, Gazova Z, Polymorphism of
lysozyme amyloid fibrils influences the cytotoxicity in
LLC-PK1 epithelial kidney cells, INTERNATIONAL JOURNAL
OF BIOLOGICAL MACROMOLECULES, Volume 65, April 2014,
Pages 176-187, (if.2.596, is.0.618) [ link
]
National and international conferences:
- Mocanu MM, Nagy P, Georgescu
L, Varadi T, Shrestha D, Baran I,
Katona E, Szollosi J, Ganea C, The
effect of flavonoids in mammary and epidermoid tumor
cells with ErbB proteins overexpression, oral
communication, 8th International Conference "Structure
and Stability of Biomacromolecules" (SSB 2013),
September 10-13, 2013, Kosice, Slovakia
- Mocanu MM, Ganea C, Siposova K,
Fillipi A, Radu E, Demjen E, Marek J, Bednarikova Z,
Antosova A, Gazova Z, Distinct fibrils morphology
induces different cytotoxicity in renal cells 8th
International Conference "Structure and Stability of
Biomacromolecules" (SSB 2013), September 10-13, 2013,
Kosice, Slovakia
- Gazova Z, Siposova K, Filippi A, Demjen E, Marek J,
Ganea C, Mocanu MM, Polymorphism of
lysozyme amyloid fibrils and cell viability, poster, 9th
European Biophysics Congress (EBSA 2013), July 13-17,
2013 Lisbon, Portugal
- M.M. Mocanu, E. Katona, M. Surcel, L.
Georgescu, T. Varadi, I. Baran, P.
Nagy, C. Ursaciuc, J. Szöllősi, C. Ganea,
Effect of flavonoids on cell cycle and apoptosis in
tumor cell lines overexpressing ErbB proteins, oral
communication, 9th National Congress of Cytometry, May
16-18, 2013, Bucharest, Romania
- Gazova Z., K. Siposova, M. Koneracka, V. Zavisova, A.
Filippi, D. Ionescu, P. Kopcansky and M.M.
Mocanu, Anti-amyloid effect of magnetic fluid
in vitro and in cells, poster, 13th International
Conference on Magnetic Fluid, January 7-11, 2013, New
Dehli, India
- Gazova Z., Siposova K., Koneracka M., Zavisova V.,
Kopcansky P., Filippi A., Ganea C., Baran I., Mocanu
M.M., Magnetic fluids attenuate the cytotoxic
effect of amyloid fibrils, poster, 22nd IUBMB & 37th
FEBS Congress, September 4 - 9, 2012, Sevilla, Spania
- M. M. Mocanu, K. Siposova, C.
Ganea, I. Baran, A. Antosova, Z. Gazova,
Protective role of nanoparticles against cytotoxic
effect induced by amyloid fibrils, XXIII Biochemical
Congress, August 26-29, 2012, Brno, Czech Republic
- M.M. Mocanu, C. Ganea, I. Baran, E.
Katona, C. Ursaciuc, M. Surcel, P. Nagy, J. Szöllősi,
Polyphenolic compounds induce the blockage of the cell
cycle progression on tumor cell lines overexpressing
ErbBs proteins, poster, ISAC XXVII International
Congress, June 23 – 27, 2012, Leipzig, Germany
- M. M. Mocanu, K. Siposova, M.
Muckova, J. Lazova, C. Ganea, I. Baran,
Z. Gazova, Magnetic fluid reverses inhibition of cell
growing caused by protein amyloid fibrils, 9th
International Conference on the Scientific and Clinical
Applications of Magnetic Carriers, May 22-26, 2012,
Minneapolis, Minnesota, U.S.A.
- A. Filippi, K. Siposova, A. Nedelcu, C. Ursaciuc, M. Surcel, A. Antosova, Z. Gazova, M.M. Mocanu, Lysozyme amyloid fibrils induce apoptosis on LLC-PK1 cells, poster, 8th National Citometry Congress, May 10 – 11, 2012, Bucharest, Romania
Latest
updated: Dec 2014
This site is updated at the end of each significant
research activity. The site's structure follows the CNCS
guidelines (December 2011)
UMF "Carol Davila" Bucharest, Disciplina de Biofizica
Bd. Eroilor Sanitari nr 8
050474 Bucharest, Romania
email: mmocanu [at] umf [dot] ro