Seribu spesies anggur terbagi menjadi dua subgenus, yaitu Euvitis dan Muscadinia.

Kebanyakan spesies yang diketahui berasal dari subgenus Euviti. Terdapat jenis anggur Eropa
dan Amerika Selatan, yang kebanyakan sulit dibedakan sehingga lebih mudah dikatakan jenis
anggur terbagi menjadi anggur merah, anggur hitam (biru kehitaman), dan anggur putih
(Tarmizi, 2010).
Flavonoid merupakan senyawa fenolik yang sebagian besar terdapat pada anggur,
yaitu sekitar 65 hingga 76%. Diperkirakan sekitar 60 hingga 70% senyawa polifenol terdapat
pada biji anggur. Antioksidan buah anggur menunjukkan efek penghambatan pada
pertumbuhan sel kanker. GSPs menunjukkan induksi apoptosis pada sel kanker paru-paru
(Zhou & Raffoul, 2012). Penelitian mengenai aktivitas senyawa fenolik ekstrak
biji

anggur

terhadap

sel

kanker

memberikan

efek

penghambatan

proliferasi sel sehingga ekstrak biji anggur dapat digunakan sebagai

pengobatan terhadap penderita kanker

Resveratrol belongs to a class of polyphenolic compounds called stilbenes. Some types of

plants produce resveratrol and other types of stilbenes in response to stress, injury, fungal
infection, and ultraviolet (UV) radiation. Food Sources: Resveratrol is found in grapes, wine,
grape juice, and

berries of Vaccinum

species including blueberries, bilberries, and

cranberries. In grapes, resveratrol is only found in the skin. This amount found in grape skins
also varies with the grape cultivar, its geographic origin, and exposure to fungal infection.
The amount of fermentation time a wine spends in contact with grape skins is an important
determinant of its resveratrol content. White and rose wines generally contain less resveratrol
than red wines, which is because the skins are removed earlier during their production,
lessening the amount that is extracted.
Resveratrol has been found to inhibit the proliferation of a variety of human cancer cell lines,
including those from breast, prostate, stomach, colon, pancreatic, and thyroid cancers when
added to cells cultured outside the body.
In animal models, there has been marked inhibition in the development of esophageal,
intestinal, and breast cancer with oral administration of

resveratrol. In mice genetically

predisposed to cancer, effects from oral resveratrol administration have been mixed.

Ann N Y Acad Sci. 2011 Jan;1215:1-8. doi: 10.1111/j.1749-6632.2010.05870.x.

Resveratrol and cellular mechanisms of cancer prevention.

Shukla Y1, Singh R.
Author information
Abstract
The use of novel and improved chemopreventive and chemotherapeutic agents for the prevention and
treatment of cancer is on the rise. Natural products have always afforded a rich source of such
agents. Epidemiological evidence suggests that a higher flavonoid intake is associated with low
cancer risk. Accumulating data clearly indicate that the induction of apoptosis is an important
component in the chemoprevention of cancer by naturally occurring dietary agents. Resveratrol, a
naturally occurring polyphenol, demonstrates pleiotropic health benefits, including antioxidant, antiinflammatory, antiaging, cardioprotective, and neuroprotective activities. Because of these properties
and their wide distribution throughout the plant kingdom, resveratrol is envisioned as a potential
chemopreventive/curative agent. Currently, a number of preclinical findings from our lab and
elsewhere suggest resveratrol to be a promising natural weapon in the war against cancer.
Remarkable progress in elucidating the molecular mechanisms underlying the anticancer properties of
resveratrol has been achieved. Here, we focus on some of the myriad pathways that resveratrol
targets to exert its chemopreventive role and advocate that resveratrol holds tremendous potential as
an efficient anticancer drug of the future.

J Diet Suppl. 2012 Mar;9(1):45-56. doi: 10.3109/19390211.2011.650842.

Resveratrol: potential as anticancer agent.

Aluyen JK1, Ton QN, Tran T, Yang AE, Gottlieb HB, Bellanger RA.
Author information

Abstract
BACKGROUND:
Cancer is one of the leading causes of deaths in the world. Current chemotherapeutic agents are
associated with serious side effects in patients therefore researchers are trying to find an alternative
agent that is effective against cancer as well as less toxic. Resveratrol (3,5,4'-trihydroxystilbene),
commonly found in red wine and grape skins, is a phytoalexin agent that was originally extracted from
the roots of Polygonum cuspidatum. Resveratrol is believed to work as a chemopreventive agent by
producing its effect on cell apoptosis, antiproliferation, and anti-inflammation.

Invest New Drugs. 2011 Apr;29(2):380-91. doi: 10.1007/s10637-009-9332-7. Epub 2009 Oct 8.

Chemopreventive doses of resveratrol do not produce

cardiotoxicity in a rodent model of hepatocellular carcinoma.
Luther DJ1, Ohanyan V, Shamhart PE, Hodnichak CM, Sisakian H, Booth TD, Meszaros
JG, Bishayee A.
Author information
Abstract
Hepatocellular carcinoma (HCC), one of the most lethal cancers, results in more than one million
fatalities worldwide every year. In view of the limited therapeutic alternatives and poor prognosis of
liver cancer, preventive control approaches, notably chemoprevention, have been considered to be
the best strategy in lowering the present prevalence of the disease. Resveratrol, a naturally occurring
antioxidant and antiinflammatory agent found in grapes and red wine, inhibits carcinogenesis with a
pleiotropic mode of action. Recently, we have reported that dietary resveratrol significantly prevents
chemically-induced liver tumorigenesis in rats. One of the mechanisms of resveratrol-mediated
chemoprevention of hepatocarcinogenesis could be related to its antiinflammatory action through
hepatic cyclooxygenase (COX-2) inhibition. Although several COX-2 inhibitors are known to exert
chemopreventive efficacy, not all are considered ideal candidates for chemoprevention due to the risk
of adverse cardiovascular events. Accordingly, the objective of the present study was to evaluate the
role of resveratrol on cardiac performance during experimental hepatocarcinogenesis initiated with
diethylnitrosamine and promoted by phenobarbital. Rats had free access to diet supplemented with
resveratrol four weeks before the carcinogen injection and 14 weeks thereafter. The cardiotoxicity of
resveratrol was assessed by monitoring the cardiac function using transthoracic echocardiography as
well as Western blot analysis of cardiac tissue. Long-term dietary administration of resveratrol dosedependently suppressed hepatic tumor multiplicity, the principal endpoint for evaluating the
chemopreventive potential of a candidate agent. The chemopreventive effects of resveratrol were also
reflected in histopathological assessment of hepatic tissues. Resveratrol did not exhibit any
cardiotoxicity but rather improved the cardiac function in a dose-responsive fashion. Our results
indicate that resveratrol-mediated chemoprevention of rat liver carcinogenesis is devoid of any
adverse cardiovascular events. Resveratrol may be developed as a chemopreventive as well as
therapeutic drug for human HCC.

Grape Seed Proanthocyanidins (GSPs)

Inhibit the Growth of Cervical Cancer by

Inducing Apoptosis Mediated by the

Mitochondrial Pathway

Qing Chen ,
Xiao-Fang Liu ,
Peng-Sheng Zheng

Published: September 4, 2014

http://dx.doi.org/10.1371/journal.pone.0107045

Abstract
Grape seed proanthocyanidins (GSPs), a biologically active component of
grape seeds, have been reported to possess a wide array of
pharmacological and biochemical properties. Recently, the inhibitory
effects of GSPs on various cancers have been reported, but their effects
on cervical cancer remain unclear. Here, we explored the effect of GSPs on
cervical cancer using in vitro and in vivo models. In vitro, the treatment of
HeLa and SiHa cells with GSPs resulted in a significant inhibition of cell
viability. Further investigation indicated that GSPs led to the dosedependent induction of apoptosis in cancer cells. The underlying
mechanism was associated with increased expression of the pro-apoptotic
protein Bak-1, decreased expression of the anti-apoptotic protein Bcl-2,
the loss of mitochondrial membrane potential, and the activation of
caspase-3, suggesting that GSPs induced cervical cancer cell apoptosis
through the mitochondrial pathway. In addition, the administration of GSPs
(0.1%, 0.2%, and 0.4%, w/v) as a supplement in drinking water
significantly inhibited the tumor growth of HeLa and SiHa cells in athymic
nude mice, and the number of apoptotic cells in those tumors was also
increased significantly. Taken together, our studies demonstrated that
GSPs could inhibit the growth of cervical cancer by inducing apoptosis
through the mitochondrial pathway, which provides evidence indicating
that GSPs may be a potential chemopreventive and/or chemotherapeutic
agent for cervical cancer.

Grape seed proanthocyanidins inhibit colon

cancer-induced angiogenesis through
suppressing the expression of VEGF and Ang1

Authors:
Shuangsheng Huang

Ninggang Yang

Yuanyuan Liu

Jing Gao

o
o

Tao Huang
Lamei Hu

Jin Zhao

Yongquan Li

Caili Li

Xiaosu Zhang

View Affiliations

Published online on: Monday, October 1, 2012

Pages: 1410-1416 DOI: 10.3892/ijmm.2012.1147
Tumor cells trigger angiogenesis through overexpression of various angiogenic
factors including vascular endothelial growth factor (VEGF) and angiopoietin 1
(Ang1). Therefore, inhibition of the expression of both VEGF and Ang1, the initial
step of tumor angiogenesis, is a promising strategy for cancer chemoprevention
and therapy. Grape seed proanthocyanidins (GSPs) are widely consumed dietary
supplements that have antitumor activity. Due to their polymeric structure, GSPs
are poorly absorbed along the gastrointestinal tract and can reach the colon at
high concentrations, allowing these chemicals to act as chemopreventive agents
for colon cancer. In the present study, we found that GSPs inhibited colon tumorinduced angiogenesis and, thus, the growth of colon tumor xenografts on the
chick chorioallantoic membranes. The mechanisms of their action were related to
inhibiting the expression of both VEGF and Ang1 through scavenging reactive
oxygen species. Previous studies have demonstrated that the chemopreventive
effects of GSPs on colon cancer are associated with their growth inhibitory and
apoptosis-inducing effects. Our results demonstrate another mechanism by
which GSPs inhibit colon tumor growth, which will be helpful for developing GSPs
as a pharmacologically safe angiopreventive agent against colorectal cancer.

Grape seed proanthocyanidins inhibit the

migration of human lung cancer cells through
the sequential inhibition of nitric oxide
synthase, guanylate cyclase and mitogenactivated protein kinase
Thejass Punathil and Santosh Katiyar
Published 1 May 2008

Article

Info & Metrics

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

Abstract
2119
Lung cancer is the leading cause of cancer related deaths in both menand women worldwide.
Therefore, it is desirable to develop newer and more effective chemopreventive agents and
strategies that can reduce the risk of lung cancer development. Grape seed proanthocyanidins
(GSPs) have been shown to exert anticancer effects in various tumor models. Chronic induction
of nitric oxide (NO), an inorganic free radical gas, has been shown to promote tumor
development and metastasis by multiple mechanisms. As NO has been shown to stimulate tumor
cell migration, a major event in metastatic cascade, our present study examined the effect of
GSPs on the signaling mechanisms underlying NO-mediated migration using metastatic-specific
non-small cell human lung cancer cells, A549, as an in vitro model. Using an in vitro transwell
migration assay, we found that treatment of A549 cells with GSPs (0, 20, 40, 60 and 80 g/ml) for
24 h resulted in a dose-dependent inhibition (26-87%) of migration of A549 cells. The migration
capacity of cells was reduced in the presence of NG-nitro-L-arginine methyl ester (L-NAME), an
inhibitor of nitric oxide synthase (NOS), and restored in the additional presence of excess Larginine (NOS substrate), confirming the role of endogenous NO as a promoter of migration.
GSPs significantly suppressed the elevated levels of endogenous NO in A549 cells in a dosedependent manner (11-56%), and also blocked the migration promoting capacity of L-arginine.
Treatment with guanylate cyclase (GC) inhibitor 1-H-[1,2,4]oxadiaxolo[4,3-a]quinolalin-1-one
(ODQ) reduced the migration of A549 cells whereas additional presence of 8-bromoguanosine
35-cyclic monophosphate (8-Br cGMP), an analogue of cGMP, restored the migration of these
cells, suggesting the role of GC in migration of A549 cells. GSPs significantly reduced the
elevated level of cGMP in A549 cells (10-62%) and also checked the migration restoring activity
of 8-Br cGMP. The mitogen-activated protein kinase kinase (MAPKK) inhibitor, UO126, inhibited
the migration of A549 cells in a dose-dependent manner, indicating the role of MAPKK in the
migration. In addition, UO126 and ODQ inhibited the migration restoring effects of L-arginine in
L-NAME-treated cells, suggesting the involvement of cGMP and MAPK pathways in NOmediated migration. Treatment of GSPs also down-regulated the phosphorylation levels of

ERK1/2 in A549 cells. Together these results indicate sequential inhibition of NO, GC and MAPK
pathways by GSPs in mediating signals for A549 human lung cancer cell migration, an essential
step in invasion and metastasis. Since NOS activity is positively associated with human lung
cancer progression, the present results are relevant for the development of GSPs as a potential
chemopreventive agent for lung cancer prevention.

American Association for Cancer Research

Grape seed proanthocyanidins inhibit the invasive potential of head and neck
cutaneous squamous cell carcinoma cells by targeting EGFR expression and
epithelial-to-mesenchymal transition

Qian Sun,
Ram Prasad,
Eben Rosenthal and
Santosh K KatiyarEmail author
BMC Complementary and Alternative MedicineThe official journal of the
International Society for Complementary Medicine Research
(ISCMR)201111:134
DOI: 10.1186/1472-6882-11-134
Sun et al; licensee BioMed Central Ltd. 2011
Received: 30 September 2011
Accepted: 21 December 2011
Published: 21 December 2011
Open Peer Review reports

Abstract
Background

Head and neck squamous cell carcinoma (HNSCC) is responsible for

over 20,000 deaths every year in United States. Most of the deaths are

due, in large part, to its propensity to metastasize. We have examined

the effect of bioactive component grape seed proanthocyanidins (GSPs)
on human cutaneous HNSCC cell invasion and the molecular
mechanisms underlying these effects using SCC13 cell line as an in
vitro model.
onclusion

The results obtained from this study indicate that grape seed
proanthocyanidins have the ability to inhibit the invasion of human
cutaneous HNSCC cells by targeting the EGFR expression and reversing
the process of epithelial-to-mesenchymal transition. These data suggest
that GSPs can be developed as a complementary and alternative
medicine for the prevention of invasion/metastasis of HNSCC cells.