International Journal of Medical Sciences

Volume 5 | Issue 1 & 2 | April & October, 2012 | 7-9

RESEARCH PAPER

Green Tea: A Natural Source of Drug for Liver Cancer

RAJESH KUMAR PATHAK AND MAMTA SAGAR
See end of the paper for
authors affiliation
Correspondence to :
MAMTA SAGAR
Department of Bioinformatics,
University Institute
of Engineering and
Technology, Chhatrapati
Shahu Ji Maharaj University,

ABSTRACT : Green tea (Camellia sinensis) has anticancer activity in animal. The HBx protein of Hepatitis
B virus activate AP-1 protein and it causes the down regulation of PTEN and p53 which are tumor suppressor
genes, leads to the tumor formation in liver. The interactions between HBx and AP-1 have been targeted by
docking of natural compounds. EGCG obtained from green tea shows highest affinity for AP-1 protein among
all natural compounds. Affinity of EGCG with AP-1 protein may be used to design drug for liver cancer.
How to cite this paper : Pathak, Rajesh Kumar and Sagar, Mamta (2012). Green Tea: A Natural Source of Drug
for Liver Cancer. Internat. J. Med. Sci., 5(1 &2) : 7-9 .

KANPUR (U.P.) INDIA

Email: mamta1060@
yahoo.com

Key Words :

Liver cancer, HBV,

Activator protein-1,
Natural compounds,
EGCG, Docking

Paper History :
Received : 15.05.2012;
Revised : 01.07.2012;
Accepted : 10.07.2012;

nticancer activity of several natural

compounds has been experimental
proved in research study. Green Tea
(Camellia sinensis) is one of them and most
popular beverage consumed in the word; it has
anticancer activity. Hepatitis B virus infection
is a leading source of liver cancer.The HBx
protein of Hepatitis B virus activate AP-1 protein
(Jacqueline Benn et al., 1996), it causes the down
regulation of PTEN and p53 gene (Wang et al.,
1994; Haviv et al.,1998). Therefore, tumor
suppressors protein are not formed, it causes
the tumor formation in liver. HBx protein plays a
regulatory role in HBV replication and is
necessary for in viral infection. It functions by
protein-protein interaction and activation of
transcription factor AP-1(Michael, 2010). When
AP-1 protein is activated by HBx protein, the
production of AP-1 protein is very high and cell
division is uncontrolled which ultimately results
in the formation of tumors in liver. Activation of
AP-1 protein is repressed by several natural
compounds, which modulate its target gene
(Rahul Amin et al., 2009). In this study docking
interactions of natural compounds EGCG,
HIND MEDICAL RESEARCH INSTITUTE

curcumin, luteoline, genistein, ellagic acid,

resveratrol, lupeol, betulinic acid, lycopene have
been studied by analysing protein- protein
interactions between HBx and AP-1. The
interactions have been targeted by docking of
natural compounds. Highest affinity of EGCG (7.97) was predicted towards AP-1 protein and
which may be involved in suppression of tumor
formation process.
Material :
Databases :
NCBI(http://www.ncbi.nlm.nih.gov/),
RCSB PDB(www.rcsb.org), PUBCHEM (http://
www.ncbi.nlm.nih.gov/pccompound). Software/
Tools:
LOOPP
Server
(http://
clsb.ices.utexas.edu/loopp/web/), GRAMM X
server (http://vakser.bioinformatics.ku.edu/
resources/gramm/grammx), PyMOL(http://
www.pymol.org/). Schrodinger- Maestro (http:/
/www.schrodinger.com).
Methods :
Structures of natural compounds have
been downloaded from Pubchem databases.

RAJESH KUMAR PATHAK AND MAMTA SAGAR

Protein-Protein docking was performed between HBx and AP1(1FOS) on GRAMM X server to predict interactions between
HBx-AP-1 proteins and finally AP-1 was docked to natural
compounds using Schrodinger software. Structure of HBx
protein was predicted by LOOPP server and structure of AP1(1FOS) was downloaded from PDB.
Natural compounds derived from natural sources (plants):
illustrate minimum free energy required for hydrogen
bonding :
Docking was carried out with natural compounds, if
energy-value is less, the protein-ligand interaction between
the compounds is higher and vice-versa. The natural
compound EGCG has greater affinity (-7.97) towards the AP-1

than other natural compounds (Table 1). Hydrogen bonds

between ECGC and amino acids serine, arginine, aspartic
acid (three hydrogen bonds) have been depicted in Fig. 1.
Curcumin, luteolin, genistein, ellagic acid resveratrol are
also showing affinity, hydrogen bonds have been predicted
in their complex with AP-1 protein but no interactions have
been predicted in lupeol, betulinic acid and lycopene.
Conclusion :
The present study shows the docking interactions of
natural compounds with AP-1 protein, these interactions may
be used for drug designing. EGCG obtained from green tea
shows maximum affinity which may be used to design a
potential drug for liver cancer.

ASP 163

GLN 166

ALA 167

ASP 170

ARG 285

LYS 282

ARG 288
GLU 284

ARG 281

SER 278

GIN 171

(A )

( B)

Fig. 1 : (A) EGCG were docked with AP-1 protein showing H-Bond interactions (yellow color) with SER 278, ARG 288 (F
chain) and ASP 163, ASP 163, ASP 170 (G chain). (B) Structure of Epigallocatechine gallate (EGCG)

Table 1: Docking results of AP-1 (G and F) chain with natural compounds

Natural compounds

Natural sources

Energy value (Kcal/mol)

EGCG

Camellia sinensis (green tea)

-7.97

Luteolin

Artichoke, broccoli, celery, cabbage, spinach, green pepper, cauliflower

-5.78

Curcumin

Curcumin longa (turmeric)

-5.67

Genistein

Soybeans and soy products

-5.59

Ellagic acid

Pomegranate juice, strawberries, barks of arjun, Lonicera caerulea.

-5.33

Resveratrol

Red wine, grapes (mainly in the skin), mulberries, peanuts, vines, pines

-5.03

Lupeol

Mango, olive, strawberry, red grapes

-4.04

Betulinic acid

Betula spp, Ziziphus spp, Syzigium spp

-3.59

Lycopene

Tomatoes, guava, rosehip, papaya,

0.29

Internat. J. Med. Sci., 5(1&2) April & Oct., 2012 : 7-9

HIND MEDICAL RESEARCH INSTITUTE

GREEN TEA: A NATURAL SOURCE OF DRUG FOR LIVER CANCER

Authors affiliations :
RAJ ESH KUMAR PATHAK, Dep artmen t of Bioinformatics,
University Institute of Engineering and Technology, Chhatrapati Shahu
Ji Maharaj University, KANPUR (U.P.) INDIA
Email: rkpathakbt@gmail.com

REFERENCES
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Shin (2009) Perspectives for cancer prevention with natural
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WEBLIOGRAPHY
Haviv, I., Shamay, M., Doitsh, G. and Shaul, Y. (1998) Hepatitis B
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Internat. J. Med. Sci., 5(1&2) April & Oct., 2012 : 7-9
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