Breast cancer is one of the most prevalent forms of cancer in women (and not unheard of in men) accounting for upwards of 15% of all cancer diagnoses. In the year 2016 over 200,000 women were diagnosed and over 40,000 died in just the United States from breast cancer. [1] If I took a poll my Steemian followers I would be willing to bet that almost all of you know someone who's life has been effected either directly or through their immediate family by this type of cancer (it has certainly had an effect on mine).

Luckily for most of us, it is one of the most treatable forms of cancer, and even when discovered in later stages (detection when stage III still has a 75% 5 year life expectancy), patients are still left with an optimistic life expectancy prognosis. [2] There are a variety of targeted therapies for certain types of cancer (those with a mutated HER2 gene) which also aide in the relatively good prognosis rates. [3] additionally therapies are available for breast cancers that are responsive to estrogen and progesterone binding [4]. However there are certain breast cancers which are not positive for mutations in HER2, nor do they grow in response to estrogen or progesterone. These breast cancers are known as Triple-Negative and as a result, there are not any targeted therapies available. Standard chemotherapy is relatively effective at battling Triple-Negative breast cancer, however the cancer often comes back and at that point chemotherapy isn't really effective any longer.[5]

However some work recently Published May 17th, 2017 in the journal Nature: Scientific Reports titled "Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells." shows that researchers are hot on the trail for changing that.

The Authors Were Testing Data Indicating An Importance of Protein Kinase C In The Growth of Triple-Negative Breast Cancer

What is "Protein Kinase C", or Even More Generally... what is a Kinase?

A kinase is a molecular machine (enzyme) in our cells that is responsible for transferring phosphate onto something (and that something may be a different molecule, or a protein).

Kinases use ATP (Adenosine Tri PHOSPHATE) as a phosphate source and transfer one of its three phosphates to its target. This transfer process is known as phosphorylation. Why might an enzyme like this be necessary? Well phosphorylation is a very prominent cellular regulatory mechanism and is used as a sort of molecular switch to turn something else on or off (depending on the target).

Protein Kinase C is one such member of this class of phosphate transfering enzymes, and its job is to transfer phosphate groups on to one of two possible amino acids (serine or threonine) in other proteins, which in-turn regulates the functioning of these target proteins like we discussed before.

Previous research has shown that heightened activity of Protein Kinase C due to increased production in breast cancer cells has a proportional relationship with the aggressiveness of the tumor growth rates (the more Protein Kinase C the tumor expresses, the more aggressively it grows). [7]

Despite this, the authors report that no studies looking into anti-cancer effects from inhibiting the function of Protein Kinase C with compounds which specifically target it and inhibit it, have been published. So that is what they set out to do here, for a compound called chelerythrine. Chelerythrine is a very specific and potent inhibitor of the activity of Protein Kinase C (meaning it doesn't inhibit other kinases, just this one).

Okay... Thats Enough Background @justtryme90... Get To The Data!

"I don't have all damn day man, get to the results!" - You Probably

Chelerythrine Stops The Growth of Triple Negative Breast Cancer Cells and Causes Apoptosis (programmed cell death)

So here we are looking at some in vitro cellular experiments where the authors tested four Triple Negative breast cancer cell lines (MDA-MB-231, BT-549, HCC1937

and MDA-MB-468) labeled TNBC and four other breast cancer cell lines (MCF7, ZR-75-1, SK-BR-3 and MDA-MB-453) labeled Non-TNBC. Up top we are looking at the cells growing in plates, the cells were treated with the chelerythrine compound (5 micro molar) and their growth monitored. They plotted the relative amounts of colonies after each time period down below. What is super apparent is just how quickly the colony counts went down for the Triple Negative breast cancer cell lines, but how the other breast cancer cell lines were not as susceptible to the compound.

Okay so the cells don't grow, is it because they are dying? Above is a graphical representation of an experiment that the authors did to look at just this. They used a technique called flow cytometry and two stains (annexin V a protein that binds to phosphatidylserine and propidium iodide a compound which binds to DNA, but only can pass through the cell membrane if a cell is dead) to tell whether the cells were undergoing apoptosis (killing themselves).

In the plot above the first four cell types are the non triple-negative breast cancer lines, and the last four are the triple-negative ones. You can see that apoptosis is induced when the compound is present ONLY for the triple-negative breast cancer cell types.

Chelerythrine slows the growth of Triple-Negaitve breast cancer cells grafted onto mice.







Okay so here we are looking at some gross pictures of mice which have had one of two tumors grafted onto them either the Triple-Negative cell line (MDA-MB-231) or a non Triple-Negative cell line (ZR-75-1). The animals were then treated with the chelerythrine compound and the growth of the tumors was monitored. We can see that the Triple-Negative cell line tumor did not grow much, while the non-triple negative tumor grew much more rapidly (though in their plot are the names flipped? The MDA-MB-231 clearly grew very little in the images but the plot makes it seem like that one got HUGE, looks backward to me :D )

Conclusions

The authors data shows that chelerythrine selectively stops the growth of triple-negative breast cancer cells.

They showed that this effect is caused by an increase in the triple-negative breast cancer cells undergoing apoptosis

They showed data illustrating that grafted tumors grew more slowly when mice were treated with chelerythrine.

The authors make a compelling case that chelerythrine (or possibly other inhibitors for Protein Kinase C) are promising for future development into a treatment for these difficult to treat triple-negative breast cancers. It is clear that much more work needs to be done, however with continued research like this perhaps even more lives can be saved from breast cancer.

Sources

All Non Cited Images Are From Pixabay.com And Are Available Under Creative Commons Licenses

Any Gifs Are From Giphy.com and Are Also Available for Use Under Creative Commons Licences

Images from figures in Nature: Scientific Reports articles are available for reuse under a Creative Commons license (all figures will be appropriately attributed and linked back to the article of reference).

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