Chemico-Biological Interactions 244 (2016) 195-203

Naringin suppresses cell metastasis

and the expression of matrix
metalloproteinases (MMP-2 and MMP-
9) via the inhibition of ERK-P38-JNK
signaling pathway in human
glioblastoma
Sonia Aroui, Bakhta Aouey, Yassine Chtourou, Annie-Claire Meunier,
Hamadi Fetoui, Abderraouf Kenani.

University of Monastir, University of Sfax, CNRS/University of Poitiers

Glioma
The most common malignant cancer which affects
Central Nervous System.

Very poor prognosis.

Rapid growth, strong invasiveness, frequent

postoperative relapse and high mortality.

Current treatments for glioma include local

irradiation, surgical extirpation and conventional
effective chemotherapeutic.

These therapies are rarely curative because of the

high proliferation rate and invasiveness gliomas
manner which always infiltrate neighboring tissues.
Cancer metastasis

The extracellular matrix (ECM) and basement membrane (BM) are the
most important physiological barriers to the metastasis of tumor cells. So,
degradation of both is a pivotal step in the cancer invasion and metastasis
process.
Extracellular Matrix
Extracelullar matrix and metastasis
Matrix metalloproteinases (MMPs)
Zn-dependent proteinases
which degrate all kind of
ECM proteins through
connective tissues and
blood vessel walls.

MMPs participate in the

progress of tumor growth,
angiogenesis, tissue
invasion and migration.
Mitogen-activated protein kinases (MAPK)

MAPK members are activated in response to different extracellular

stimuli and have distinct downstream targets, thus serving different
roles in celular responses.

Extracelular signal-regulated kinase 1 and 2 (ERK 1/2)

c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK)

p38 MAPK

Associated with increased scattering/motility, invasion, proliferation,

survival and morphogenesis.

MAPK play a central role in regulating the expression of MMPs

Mitogen-activated protein kinases (MAPK)
Naringin
Naringin (4,5,7-Trihydroxyflavanone-
7-rhamnoglucoside) is found in
grapefruit and is related to citrus herbs
species.

It has an extensive spectrum of

pharmacological activities such as anti-
inflammatory, anti-oxidant
antitumoral and neuroprotective
effects.

Naringin interacts with several cell

receptors to modulate the
expression of the downstream
signalling molecules in several cancer
Aim
Examine the inhibitory effects and the related signaling pathways of
naringin on the invasion and migration of the human glioblastoma U87
cancer cells in vitro.
Results MTT assay

Trypan blue assay

Results
Effects of naringin on cell viability and cell cycle distribution in
glioma cells.
Fig. Fig.
1 2
Results

Invasion assay Transwell migration

assay
Results
Naringin inhibits the migration and invasion of U87 GBM cells.
Fig.
3 Fig.
4
Results
Fig.
5
Results

Western Blot
Zymography
Results
Naringin inhibits activity and protein expressions of MMP-2 and -9
in U87 GBM cells.
Fig. Fig.
6 7
Results
Naringin inhibits the phosphorylation of JNK, ERK and p38
pathways.
Fig.
8
Conclusions
Apoptotic effect of flavonoids
Luteolin , Naringin and Quercetin in
squamous hypopharyngeal cancer
cell line FaDu
Ricardo Gonzlez Salguero
Tutoress: Dra. Gloria Gutirrez Venegas
 Head and neck cancer
Larynx, throat, lip, mouth, nose and
salivary glands.
This cancer starts in the squamous cells,
which cover wet surfaces.
3% of cancers in the United States
(52,000 cases in 2012).

Pharyngeal cancer

Causes: Symtoms:
Alcohol and tobacco use Difficulty to breath or speak
Infection of human papilloma virus Pain when passing
(HPV-16) Permanent pain in the neck or throat
Poor oral hygiene Frequent headaches,
Use of mouthwashes with high Pain or ringing in the ears
alcohol content. Difficulty to hear
Flavonoids
Plant secondary metabolites

Luteolin

Naringin

Quercetin
Objetive
Objetive:
Determine whether flavonoids Luteolin, Naringin and Quercetin induce cell
death by apotosis in FaDu cell line.

Aims:
1. Determine the apoptosis via induced by flavonoids Luteolin, Naringin
and Quercetin in FaDu cell line.
2. Determine if Luteolin, Naringin and Quercetin induce Cytocrome C
traslocation from mitochondria to cytoplasm.
3. Determine if Luteolin, Naringin and Quercetin induce DNA degradation
in FaDu cell line.
Results: Luteolin
CYTOTOXICITY
Results: Luteolin
APOPTOSIS INDUCTION
Results: Luteolin
DNA DEGRADATION
Luteolin (100 M)

Basal 2 4 6 20 24
(h)
Results: Naringin
CYTOTOXICITY
Results: Naringin
APOPTOSIS INDUCTION
Results: Quercetin
CYTOTOXICITY
Results: Quercetin
APOPTOSIS INDUCTION
Results: Quercetin
DNA DEGRADATION

Quercetin (100 M)
Basal 2 4 6 20 24
(horas)
Universidad Nacional Autnoma de Mxico

Facultad de Qumica

Activation of MAPK via in

cardiomyocyts H9c2 stimulated with
flagelin and the regulatory efects of
Luteolin

Ricardo Gonzlez Salguero

Tutoress: Dra. Gloria Gutirrez Venegas

 Introduction
Periodontal disease is a chronic inflammatory disorder that affects surrounding and holding tissues of the
tooth.
It is associated with microorganisms that form subgingival plaque.
It contributes to the development of extraoral diseases when they reach the bloodstream as infectious
endocarditis, characterized by an exaggerated immune response of the heart valves after PAMP's recognition
by TLR.
RESULTS
1 2

Activation of MAPK via by flagelin over time

3 4

Effect of luteolin in MAPK via activated by flagelin

RESULTS

Evaluation dose-response of flagelin in Evaluation dose-response of luteolina

transcription of COX-2. in the transcription of COX-2 induced
by flagelin.
RESULTS

Effect of flagelin and luteolin in viability of cells H9c2.