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A ‘phytochemical super-cocktail’ containing six natural compounds neutralises cancer cells in test tube experiments. A mixture of curcumin, resveratrol, genistein, indole-3-carbinol, C-phycocyanin and quercetin halts the growth of breast cancer cells, causes them to commit suicide and robs them of the ability to spread through the body, write researchers from Sultan Qaboos University in Oman in the Journal of Cancer.

We have already written about work that these researchers are doing: about the cancer inhibiting effect of Spirulina platensis. The researchers reported that an extract of this green-blue cyanobacteria protected lab animals against breast cancer.

In the study mentioned here, the researchers tested the joint effect of six compounds, all of which have shown a cancer-inhibiting effect in cell and animal studies. First author Allal Ouhtit calls the combination a ‘phytochemical super-cocktail’. The composition of the cocktail is shown below, along with the concentrations used. All of these can occur in the human body.

1

The researchers studied the effect of the individual components of the mix, plus their combined effect, on the human breast cancer cell lines MCF7 and MDA-MB-231. The latter is the most harmful as this cell type is not sensitive to hormones. Hormone-sensitive cancer cells can be treated by using hormone therapy; types that are not sensitive to hormones cannot be treated in this way.

The figure below shows that separately the components – except for indole-3-carbinol – did not have much effect on the growth of cancer cells. But the ‘super-cocktail’ reduced the growth of both types of cell after just a few days of exposure. The figure below shows the results for the MCF7 cells. The MDA-MB-231 cells reacted almost identically.

2

The longer the exposure to the cocktail, the more cancer cells died. [Apoptosis = cell death] The hormone-sensitive MCF7 cells were particularly vulnerable.

The combination of plant substances reduced the ability of the cancer cells to spread themselves in other, healthy cells [Relative invasiveness] by 80 percent.

3

When the researchers examined the cancer cells at molecular level, they discovered how the combination of plant substances neutralised the cancer cells. One thing that the combination did was to reduce the synthesis of the protein CD44. Cancer cells use this protein when they spread through healthy tissue.

MCF7 cells are still capable of producing the tumour-inhibiting protein p53. When healthy cells are under pressure, they produce more p53. As a result, cells stop developing and give priority to repair processes. If the DNA has been damaged, p53 helps a cell to repair this. If this doesn’t work, p53 causes the cell to commit suicide. The ‘super-cocktail’ boosted the production of p53 in MCF7 cells by a factor 29 [below left].

4

In MDA-MB-231 cancer cells the p53 gene is damaged. As a result these cancer cells produce a perverted protein: one that strengthens the cancer cells rather than causing them to commit suicide. The combination of plant substances reduced the synthesis of this protein in the MDA-MB-231 cells [above right].

You’d expect that supplements containing components from the cancer-inhibiting cocktail could offer humans protection against cancer. The researchers want to do experiments to find out whether this is the case. On lab animals.

Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: genes that underpin its mode of action.

Abstract

Traditional chemotherapy and radiotherapy for cancer treatment face serious challenges such as drug resistance and toxic side effects. Complementary / Alternative medicine is increasingly being practiced worldwide due to its safety beneficial therapeutic effects. We hypothesized that a super combination (SC) of known phytochemicals used at bioavailable levels could induce 100% killing of breast cancer (BC) cells without toxic effects on normal cells and that microarray analysis would identify potential genes for targeted therapy of BC. Mesenchymal Stems cells (MSC, control) and two BC cell lines were treated with six well established pro-apoptotic phytochemicals individually and in combination (super cocktail), at bioavailable levels. The compounds were ineffective individually. In combination, they significantly suppressed BC cell proliferation (>80%), inhibited migration and invasion, caused cell cycle arrest and induced apoptosis resulting in 100% cell death. However, there were no deleterious effects on MSC cells used as control. Furthermore, the SC down-regulated the expression of PCNA, Rb, CDK4, BcL-2, SVV, and CD44 (metastasis inducing stem cell factor) in the BC cell lines. Microarray analysis revealed several differentially expressed key genes (PCNA, Rb, CDK4, Bcl-2, SVV, P53 and CD44) underpinning SC-promoted BC cell death and motility. Four unique genes were highly up-regulated (ARC, GADD45B, MYLIP and CDKN1C). This investigation indicates the potential for development of a highly effective phytochemical combination for breast cancer chemoprevention / chemotherapy. The novel over-expressed genes hold the potential for development as markers to follow efficacy of therapy.

PMID: 24312140 [PubMed] PMCID: PMC3842439

Source: http://www.ncbi.nlm.nih.gov/pubmed/24312140

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