Brazilian Funding - Prof Dr Beny Spira, USP Brasil
Here are some of the updates received from the research in Brazil:
3 November 2004
Glutathione-S-transferase (GST) is a family of cellular proteins whose primary function is to neutralize toxic and carcinogenic compounds produced
endogenously by the cells or that are imported from the environment. GST is therefore important to prevent the deleterious effects of toxic compounds
that, among other things, might cause mutations in cell's DNA, leading sometimes to cancer. A healthy person should therefore express high amounts of
GST in his cells in order to get protection against such potentially dangerous compounds. On the other hand, people who are affected by malignant
tumours may acquire resistance to chemotherapy as a result of excess GST expression in the tumour cells. In this case, it would be desirable to inhibit
GST so as to increase the efficiency of chemotherapy.
 Our group is screening Brazilian medicinal plants that may affect, either positively or negatively, the expression level of GST. In the past year,
we tested the effect of 19 different plants on the activity of GST of human leukaemia cells (Jurkat lymphocytes). Plants were collected from the
Atlantic rain forest in the southern part of the state of Sao Paulo. They were dried, ground and the active compounds were extracted with methanol.
Seven plants significantly increased the expression of GST, while nine other inhibited its activity. Three plants had no effect on GST under the
concentrations tested. It should be noticed that among those plants that inhibited GST, some were also very toxic, killing the majority of the cells
when administered at high concentrations.
July 2006
The effect of Brazilian medicinal plants on the expression and activity of glutathione-S-transferase - Part 2
 In the first part of the project we collected the leaves of 26 plants from the Atlantic rain forest in the state of Sao Paulo and extracted most
of their molecules by macerating the dry and grinded leaves with methanol. The effect of these 26 methanolic extracts on the activity of GST of
hepatocytes (liver cells) and leukaemia cells was tested. Several extracts increased, while others inhibited the activity of the GST enzyme.
In this part of the project we will focus on the plants that strongly inhibited GST of leukaemia cells, as these could be used in the future as
adjuvants of leukaemia treatment. Since methanolic extracts contain a large quantity of molecules, and since most of them being probably inert in
relation to GST, we would go a step further and fractionate the methanolic extracts to find out what molecule(s) is/are actually involved in the
effect on GST. An expert on plant extract fractionation, Dr. André Konan, who has just finished his Ph.D. in the University of Sao Paulo, will work
on this.
We will also test the combined effect of the plant extract fractions and arsenic trioxide, which is a drug used to treat certain types of leaukaemia.
This combination is necessary, because, unfortunately, the most common type of children leukaemia (Acute Lymphoblastic Leukaemia or ALL) is resistant to
this drug due to the presence of GST in the tumour cells. We hope that by inhibiting GST in ALL cells, they would become suceptible to arsenic trioxide
treatment.
Report no. 3
Abstract for the general audience
In the last year, there were big changes in the laboratory. Our technician Cassia Principe has finished her work with us. She is now writing her
MSc thesis, which is based on her work on this project and is due to submit her thesis by April this year.
 Dr. Andre Konan is now working on the project. Dr. Konan has recently finished his PhD working on the effect of cashew leaves (Anocardiumm
occidentale) on ulcer. He brought to this project his expertise on medicinal plants and also extracts of cashew leaves whose effect on leukaemia
cell are reported here. He found out that an alcoholic extract of cashew leaves inhibited GST activity and also displayed a strong anti-proliferative
effect on leukaemia cells. Some sub-fractions of this extract retained these effects, suggesting that we are in the correct path towards the
identification of the active components in the cashew leaves extract. A preliminary attempt to identify the compounds presented in one of these
fractions, showed it is composed by some polyphenols. Polyphenols are chemical substances normally found in plants which have antioxidant
characteristics and possible health benefits.
We also continued our research on other medicinal plants that have been previously studied throughout this project. From the initial 24, we narrowed
down to the 4 more promising plants. The extract of one of this plants, Cecropia pachystachya, was fractionated and found to inhibit GST
activity and cell proliferation. The methanolic extract of another plant, Bauhinia forficata, also displayed anti-proliferative activity
against leukaemia cells. It also showed an additive effect when combined with the standard anti-leukaemia drug arsenic trioxide.
Our next steps will be to further fractionate the extracts of Cecropia pachystachya and Bauhinia forficata and to look for their
effect on cell proliferation and GST activity. The mechanism of by which the plant extracts inhibit cell proliferation will also be studied as well as
the combined effect of the plant extracts and arsenic trioxide on leukaemia cells.
December 2009
The paper about about Cassia's work is finally out, view the summary of the paper.
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