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Anggur/Grape (Vitis vinifera)

anggur_grape_ccrc_ugm

Figure 1. Grape (Vitis vinifera)

1. Name of Plant

Name : anggur (grape)

2. Classification of Plants

Kingdom: Plantae

Divisio : Spermatophyta

Subdivisio : Angiospermae

Class: Magnoliopsida

Subclass : Rosidae

Ordo : Rhamnales

Family: Vitaceae

Genus:  Vitis

Species: Vitis vinifera, Vitis labrusca

3. Description Plants

Shrubs vines, length can reach 10 m, curved round leaves with serrated edge and tapering ends. Flowers are arranged in panicles. Fruit round or slightly oval-sized +/- 2 cm, smooth-skinned, color variety, sweet fruit sour meat, containing 2-4 seeds. Not all types of genus Vitis edible, which can be eaten only two types, there are Vitis vinifera and Vitis labrusca. Plants grape type Vitis vinifera has the following characteristics:

a) Thin skin, sweet and fresh taste.

b) The ability to grow from lowland up to 300 m above sea level dry climates.

c) Including this type, there are Gros Colman, Probolinggo Biru dan Putih, Situbondo Kuning, Alphonso Lavalle and Golden Champion.

Plants grape type Vitis vinifera has characterized:

a) Thick skin, sour taste, and less fresh.

b) The ability to grow from lowland up to 900 m above sea.

c) Including this type is Brilliant, Delaware, Carman, Beacon and Isabella.

4. Ingredients and Benefits of Plants

Trans-Resveratrol(trans-3,5,4′-Trihydroxystilbene;3,4′,5-Stilbenetriol(trans-Resveratrol; (E)-5-(p-Hydroxystyryl)resorcinol (E)-5-(4-hydroxystyryl)benzene-1,3-diol.

Grapes used as fresh fruit or for processing into other products as like beverage fermented grape juice results that contain alcohol so-called Wine, dried into raisins and for industrial purposes jams and jellies.

5. Mechanism of Anticancer Research

In vitro studies aimed at determination of the molecular mechanisms of the effects of resveratrol (RES) on the process of apoptosis in retinoblastoma cells, has been implemented by using a model of human retinoblastoma Y79 cells and Neoroblastoma cells SK-N-AS as a comparison. As the beginning step was measured Y79 cell viability determined using the fluorescent base assay techniques. Furthermore, the effects of anti-proliferative and pro-apoptotic determined using the Hoechst stain 33258 followed by flow cytometry. Trans-membrane mitochondrial potential changes thought to determine the release of cytochrome-c. The decrease in the value of the transmembrane potential mitokondia determined as a function of drug treatment using 5,5’, 6,6’, -tetrachloro-1,1’, 3,3’-tetraethylbenzamidazolocarbocyanin iodide (JC-1). Qualitatively release of cytochrome-c from mitochondria determined by immunoblotting. While the enzyme activity of caspase-9 and 3 determined through its ability to break down a substrate peptide flourogenic enzyme value of the activity is expressed in units of RFU (Relative fraction unit).

Effect of antiproliverative RES initiated with cell cycle arrest terinduksinya and continue the process of apoptosis. The escape of cytochrome-c from the inner mitochondrial membrane occurs when mitochondrial trans-membrane potential changes (∆Ψm). RES has also been identified inhibits the activity of several enzymes associated carcinogenesis as:

1. Enzyme-enzyme of mitochondrial electron transport chain:

a. NADH/ubiquinone oxidoreductase (complex-1) Fang & Casida (1998),

b. F0-F1 ATP-ase (Zheng & Raminez, 2000; Kipp & Raminez, 2001; Gledhill & Walker, 2005),

2. Cellular enzymes such as:

a. DNA Polymerase α and β (Stivilla et al., 2001, Locatelli et al., 2005),

b. Cyclooxigenases (COX-1 & COX-2)( Jang et al, 1997; Szewczuk, Forti, Stivalia, Penning, 2004)

c. Human cytochrome-c P450 isoenzymes : CYP 1A1 (Chun, Kim, Guengerich, 1999).

d. NRH/quinone oxidoreductase 2 (NQO2=NAD(P)H quinone oxidoreductase 2)/quinone reductase-2(QR-2). This enzyme will establish flavoprotein complex with resveratrol (Buryanovskyy et al., 2004) so will reduce metabolism quinnone and its derivatives to protect cells from redox cycle and oxidative stress (Iskander and Jaiswal).

This research is the first research who studied the effects of chemotherapeutic RES in the apoptosis mechanism on the cell line RB in vitro. Expected the results of this research can inspire clinicians in the management of Rb with the chemopreventive approach which is owned by natural compounds or its synthetic later.

Some studies suggest that RES has anti-proliferative activity and pro-apoptotic effects in several tumor cell lines. Nevertheless molecular mechanisms anti-tumor role of RES has not been well identified.

The results of this research indicate that:

Provision of RES in concentrations and different time periods are able to induce apoptosis. This is supported by apoptosis cell morphology: chromatin condensation, increasing population sub-G1 cell fraction.

Anti-proliferative RES indicated by increasing population cell fractions S (phase synthesis) compared with control without treatment (UNT). In previous research with other tumor cell lines, found that RES can inhibit catalytic activity of the enzyme COX-1 and COX-2 tumor promoting and can inhibit DNA synthesis by holding direct interaction with DNA polymerase α and β (Stivilla, et al., 2001) from here it is known that RES is able to block cell cycle progression. In in vivo research RES suppress the expression of COX-2 regulation by inhibiting the activity of factor transcription NF-κB (Banerjee, Bueso-Ramos, Aggarrwal, 2002).

Induksi RES pada pelepasan sitokrom-c, peningkatan aktivitas caspase-9 dan caspase-3 merupakan indikasi kuat teraktivasinya proses apoptosis. Aktivitas jalur intrinsik dan ekstrinsik apoptosis akan meningkat akibat induksi RES (Fulda and Debatin, 2005; Dorrie, Gerauer, Watcher and Zunino, 2001). Pada penelitian ini RES diketahui mampu menurunkan nilai potensial membrane mitokondria secara signifikan, hal ini mengindikasikan bahwa penurunan potensial trans membrane mitokondria merupakan tahap awal dari RES-induced apoptosis.

Potential value reduction of mitochondrial membrane (∆Ψm) not associated with inhibition of expression NQO2. The absence of NQO2 in mitochondria, inhibition of expression in Y79 cells, and the sensitivity of cells to signaling potential of apoptotic RES indicates that there are other alternatives RES target molecules are located in the mitochondria.

The escape of cytochrome -c from mitochondria inner membrane, it needs assistance from factors that are as cytosolic components. It has been widely known that Bax is a protein which induces the release of cytochrome-c. Research of Mahyar-Roemer, Kohler & Roemer (20020 reported that RES is able to induce the expression Bax-independent mitochondrial apoptosis. Reported by Pozo-Guisado, Merino, Mullero-Novaro, et. al.(2005), that RES is able to suppress regulation of protein expression anti-apoptotic BCl2 and BCl-XL.

Potential pro-apototic RES increasingly described with an increase in caspase-9 and caspase-3 enzyme activity in solving peptide flourogenic which resemble with natural substrate of both enzyme.

Conclusions :

RES is able to induce the apoptosis intrinsic pathway played by mitochondria with :

a. Lowering the mitochondrial transmembrane potential (Δψm).

b. Enhance the release of cytochrome -c.

c. Increasing activity of caspase 9.

d. Increasing activity of caspase 3

 

References:

Sareen, D., Paul R. van Ginkel, Jennifer C., Takach, Mohiuddin, A., Darjatmoko, S.R., Daniel M., Albert, and Polans A.S., 2006, Mitochondria as the Primary Target of Resveratrol-Induced Apoptosis in Human Retinoblastoma Cells, Investigative Ophthalmology and Visual Science, 47 (9):3708-3716

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