PGV-0 Inhibits Breast Cancer Cells

Breast cancer is the number two deadly disease after cervical cancer. Various efforts have been made to fight the disease. Now radiation therapy and cytostatics have the possibility of inhibiting the spread of cancer.

Breast cancer and cervical cancer are types of cancer with the highest frequency of occurrence among other types of cancer that affect women.In Indonesia, the number of patients with breast cancer ranks second after cervical cancer.

Breast cancer is the leading cause of death in women in various parts of the world.Because of this, it is necessary to work hard to fight cancer by selectively inhibiting and killing its cell growth, accompanied by efforts to minimize side effects.

The formation of cancer through four stages. 

At the initiation stage, DNA damage or mutation occurs, which regulates cell multiplication by cancer-causing compounds (carcinogens). Furthermore, there is an increase in abnormal cell multiplication due to the initiation process. This phase is called the promotion stage.

The appearance of malignant cancer cells followed by obvious genetic changes marks the developmental stage of progression. In the metastatic stage (stage four), cancer cells expand to other tissues through blood vessels or lymph vessels. The expansive cell will form a secondary tumor in the infected tissue.

While attacking the normal cells around it, the cancer also produces toxins and releases cancer cells from their mother cells which rupture. These toxins and cancer cells will spread with the bloodstream. Because of this, cancer is often found growing elsewhere as a result of its metastases. In severe cancer, bleeding often occurs.

Specific drugs to stop the development of cancer cells have not yet been found. At present prevention efforts continue to be attempted with radiation therapy and cytostatics.

Moving on from that thought, Dr. Edy Meiyanto Msi Apt, a researcher from CCRC (Cancer Chemoprevention Research Centre), conducted a study to obtain a more stable structure with better activity than curcumin in inhibiting the growth of breast cancer cells (T47D cells).

"The research development carried out by CCRC is focused on modifying the molecular structure of curcumin to obtain better pharmacological activity," explained Edy, who is now deputy dean 1 of the UGM Faculty of Pharmacy.

To confirm the results of this research conducted in mid-2006, in September 2006 an international symposium was also held to discuss the effect of curcumin modification, one of the analogues of which was the result of this research, namely Pentagamavunon-0 or 2,5-bis (4'-hydroxy-3 '-methoxy-benzylidene)-cyclopentanone (PGV-0).

In conducting this research, Edy was not alone. Supardjan AM MS Apt, a researcher who is also a UGM pharmacy lecturer, played a role in synthesizing and eluding the structure of curcumin so that a new analogue with a more stable structure was obtained, namely PGV-0.

Triggering Apopotosis of Cancer Cells 

Early in this study used a cytotoxicity test with the MTT method. Namely, the cell suspension in the medium was put into plate 96 and incubated for 24 hours in a carbon dioxide (CO2) incubator. At the end of incubation, the medium in each well was removed and washed with a certain kind of solution. Then, the plate was incubated at 37 degrees Celsius. Live cells will react with MTT to form formazan purple color. The next process, an observation test of cell proliferation kinetics was carried out. Cell proliferation is a function of the cell recycling program. The method was carried out in the same way as the cytotoxicity test with different treatment concentrations at 6, 12, 24, 48, and 72 hours.

Both tests in this research use methods to determine the potential of PGV-0 as an anti-proliferative compound against breast cancer cells. MTT is absorbed into living cells and broken down through a reduction reaction by the enzyme reductase.

In addition, this study obtained data regarding cell proliferation indicating that both PGV-0 and curcumin could inhibit or reduce the proliferative properties of breast cancer cells. However, at certain concentrations, curcumin induced no effect on the level of living cell changes.

It also shows that PGV-0 has a stronger effect on inhibiting breast cancer cell proliferation than curcumin.

Another advantage of PGV-0 is its structure. With a flatter structure than curcumin, it allows PGV-0 to have better activity. PGV-0 is also able to inhibit cell cycle which also results in the acceleration of apoptosis (suicide program) of breast cancer cells.

PGV-0 and also kukumin have the same function, which is lever blocking the growth of new blood vessels. The substance is capable of acting as an immunomodulator or immunostimulator, or able to increase the number of lymphocytes, increase cancer killing, and increase specific antibodies.

Inhibition in Certain Phases
Based on cytotoxicity tests and cell growth profile observations proved that the cytotoxic potential and proliferation inhibition of breast cancer cells, compound PGV-0, is better than curcumin.

This growth inhibition occurs because the compound causes cell death or inhibits the cell cycle progression program (cell development) into cell cycle arrest. PGV-0 can trigger cell death through apoptosis or cause cell cycle arrest as curcumin has been tested on several cancer cells.

Analysis of BrdU incorporation proved that PGV-0 was able to inhibit cells from entering S phase more strongly than curcumin. These obstacles can occur in the G1 phase (Gap1) or S phase (the phase of DNA synthesis and replication).

Breast Cancer Begins From Abnormal Cells
When did breast cancer start to spread? When there is an abnormal growth of cells in the mammary glands or ducts of the glands. Also, it can originate from the supporting tissues of the breast.

Cancer occurs when the DNA of normal cells is damaged, causing genetic mutations. If it is not corrected immediately, the multiplication of cells whose DNA is damaged has the potential to produce cancer cells. Whereas cell multiplication is intended to restore cells that are worn out or damaged.

If normal cell DNA damage is not prevented by compounds or vitamins and minerals that are anti-oxidants or when cancer cells have already formed, suppression of the growth of these cancer cells must be immediately carried out.

To inhibit the metastasis (spread) of cancer cells, it must be known how these cells spread. There are two ways for cancer cells to metastasize, namely through angiogenesis (the formation of new blood vessels) and the destruction of collagen which is the framework for normal cells.

Thus, metastasis will be inhibited if angiogenesis can be prevented, while damaged collagen can be repaired by the body by utilizing certain foods.

For angiogenesis, cancer cells release growth factors. It turns out that the production of growth factors can be inhibited by curcumin which is contained in turmeric, temulawak, white turmeric, and PGV-0 as an analogue.

Symptoms to Watch Out
For However, what needs to be considered is that this type of cancer often goes unnoticed. The occurrence of gene mutations due to these abnormal cells is triggered by a foreign substance that enters the body, such as food preservatives, MSG, radioactive, oxidant, or carcinogenetic substances that are produced naturally by the body.

Together with blood flow and lymph flow, cancer cells and the toxins they produce can spread throughout our body such as bones, lungs and liver.

Therefore, initially in breast cancer patients found lumps in the armpits or other lymph node lumps. In fact, cancer of the liver and lungs also appeared as metastases.

It is highly recommended to detect it by means of sarari or breast self-examination to anticipate breast cancer. Moreover, the cancer is often found at an advanced stage. Sasari is the simplest and easiest way to do, but has important meaning for early detection of breast cancer.

Be Aware for Early Detection
How to prevent breast cancer? Cancer researcher at the Faculty of Medicine, Yarsi University, Jakarta Dr. Susi Endrini MSc said, check your breasts, avoid fatty foods, and consume fruits and vegetables that are rich in antioxidants. What is the process and causes of the growth of breast cancer cells?

Medically, breast cancer cells grow through three stages. First, initiation or triggering. Second, promotion. Cancer cells multiply by spreading. The third stage, which is dangerous, is the progressive phase. At that time, the cells have attacked other organs through blood vessels. Factors that trigger the growth of cancer cells, among others, chemicals, food, and viruses. It could also be genetic factors and radiation.

How is it treated?
There are several options. Can with irradiation. When the cancer cells have entered stage 3 or 4, the tumor is removed surgically. Another treatment option is chemotherapy, including drugs. You can also do a combination of these options.

What do you think about using PGV-0, which is a curcumin analogue, as a breast cancer drug?
Research on the inhibition of cancer cells through Pentagamavunon (PGV-0) as a curcumin analogue (the active ingredient of Temu buffoonery) has the potential to be further developed. It was proven in that study, PGV-0 was able to inhibit T47D cells which are breast cancer cells.

Can PGV-0 cure and minimize side effects?
Minimizing side effects depends on the reaction to the patient's normal body cells. To be sure, usually, cancer sufferers will experience hair loss as in chemotherapy treatment.

How to prevent the disease? 

For prevention, it can be done early "realize" (self-examination) or "sarari" (self-examination of the breasts). This can be done after every shower. Then, avoid eating fatty foods. It is recommended to eat fruits and vegetables that contain antioxidants.