Ursolic acid inhibits growth of mCRC in mice

peterz54

Published in Clinical Cancer Research, July, 2012.

Ursolic Acid Inhibits Growth and Metastasis of Human Colorectal Cancer in an Orthotopic Nude Mouse Model by Targeting Multiple Cell Signaling Pathways: Chemosensitization with Capecitabine.

Prasad S, Yadav VR, Sung B, Reuter S, Kannappan R, Deorukhkar AA, Diagaradjane P, Wei C, Baladandayuthapani V, Krishnan S, Guha S, Aggarwal BB.


Source

Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center.


Abstract

PURPOSE:

Development of chemoresistance, poor prognosis, and metastasis often renders the current treatments for colorectal cancer (CRC) ineffective. Whether ursolic acid (UA), a component of numerous medicinal plants, either alone or in combination with capecitabine, can inhibit the growth and metastasis of human CRC was investigated.

EXPERIMENTAL DESIGN:

The effect of UA on proliferation of colorectal cancer cell lines was examined by mitochondrial dye-uptake assay, apoptosis by esterase staining, NF-κB activation by DNA binding assay and protein expression by western blot. The effect of UA on the growth and chemosensitization was also examined in orthotopically-implanted CRC in nude mice.

RESULTS:

We found that UA inhibited the proliferation of different colon cancer cell lines. This is correlated with inhibition of constitutive NF-κB activation and downregulation of cell survival (Bcl-xL, Bcl-2, cFLIP, survivin), proliferative (Cyclin D1), and metastatic (MMP-9, VEGF, ICAM-1) proteins. When examined in an orthotopic nude-mice model, UA significantly inhibited tumor volume, ascites formation and distant organ metastasis, and this effect was enhanced with capecitabine. Immunohistochemistry of tumor tissue indicated that UA downregulated biomarkers of proliferation (Ki-67) and microvessel density (CD31). This effect was accompanied by suppression of NF-κB, STAT3, and β-catenin. In addition, UA suppressed EGFR, and induced p53, and p21 expression. We also observed bioavailability of UA in the serum and tissue of animals.

CONCLUSIONS:

Overall our results demonstrate that UA can inhibit the growth and metastasis of CRC and further enhance the therapeutic effects of capecitabine through suppression of multiple biomarkers linked to inflammation, proliferation, invasion, angiogenesis, and metastasis.


From Wikipedia:
Ursolic acid is present in many plants, including apples, basil, bilberries, cranberries, elder flower, peppermint, rosemary, lavender, oregano, thyme, hawthorn, and prunes. Apple peels contain large quantities of ursolic acid and related compound

More on Usolic acid

janie1

Thanks Peter.
Seems like
Thanks Peter.

Seems like all these research centers clinical trials are combining something (new agent) with a current chemo. Sadly, this one combines the new agent with Xeloda. More of the same again. People can't take the same chemo forever, and I doubt this will be a cure, but just another "add a couple of months to your life" scenario.....even if it would come to fruition in the next decade.

I wish that I were wrong......oh boy do I wish.... But what a tragedy this is where the billions of free research money is mainly going.

Does it bother anyone else that so many clinical trials are utilizing a current (toxic) chemo with.....whahoo......something new & different.

pete43lost_at_sea

thanks peter
Awesome.

Hugs,
Pete

peterz54

janie1 said:

Thanks Peter.
Seems like
Thanks Peter.

Seems like all these research centers clinical trials are combining something (new agent) with a current chemo. Sadly, this one combines the new agent with Xeloda. More of the same again. People can't take the same chemo forever, and I doubt this will be a cure, but just another "add a couple of months to your life" scenario.....even if it would come to fruition in the next decade.

I wish that I were wrong......oh boy do I wish.... But what a tragedy this is where the billions of free research money is mainly going.

Does it bother anyone else that so many clinical trials are utilizing a current (toxic) chemo with.....whahoo......something new & different.

it bothers me
it bothers me that I am billed $18,000 per cycle for Avastin and oxaliplatin, and their beneifit is in terms of a few months of life, with side effects. 10s of billions of dollars per year on this stuff.

and while i see quite a lot of research by reputable organizations on plant extracts, much of which suggests positive benefits, it seems there are still large gaps in our knowledge. Much more work needs to be done to undertand how these plant extracts work, what the optimal doses are, and how they should be delivered.

omrhill

"Orthotpic Nude Mouse Model"
Ummmmm..... aren't all mice nude? ;-)

pete43lost_at_sea

peterz54 said:

it bothers me
it bothers me that I am billed $18,000 per cycle for Avastin and oxaliplatin, and their beneifit is in terms of a few months of life, with side effects. 10s of billions of dollars per year on this stuff.

and while i see quite a lot of research by reputable organizations on plant extracts, much of which suggests positive benefits, it seems there are still large gaps in our knowledge. Much more work needs to be done to undertand how these plant extracts work, what the optimal doses are, and how they should be delivered.

only 18k pet cycle, what a bargain
My diet, supplements and potions are looking cheap.

Big pharma is the most profitable sector of the fortune 500.

Those huge profits are needed to keep our Western societies running.

I am stealing my kids Apple skins and adding them to my smoothie tonight.

Keep the good info coming.

I told my alt doc today about ursolic acid, he looked at me like I was a genius.

No one has ever done that before.

Hugs,
Pete

Ps it's a great name Pete, it means rock but on can it's going to be remembered for nature. I hope.
Only nature heals in my opinion.

Sundanceh

omrhill said:

"Orthotpic Nude Mouse Model"
Ummmmm..... aren't all mice nude? ;-)

Mickey and Minney Mouse
Nope:)

peterz54

pete43lost_at_sea said:

only 18k pet cycle, what a bargain
My diet, supplements and potions are looking cheap.

Big pharma is the most profitable sector of the fortune 500.

Those huge profits are needed to keep our Western societies running.

I am stealing my kids Apple skins and adding them to my smoothie tonight.

Keep the good info coming.

I told my alt doc today about ursolic acid, he looked at me like I was a genius.

No one has ever done that before.

Hugs,
Pete

Ps it's a great name Pete, it means rock but on can it's going to be remembered for nature. I hope.
Only nature heals in my opinion.

That's great
as an aside, I recognised one of the author's name (BB Aggarwal ) who has done other work on plant extracts (like curcumin) at MD Anderson, considered teh number 1 cancer center in the US.

peterz54

pete43lost_at_sea said:

only 18k pet cycle, what a bargain
My diet, supplements and potions are looking cheap.

Big pharma is the most profitable sector of the fortune 500.

Those huge profits are needed to keep our Western societies running.

I am stealing my kids Apple skins and adding them to my smoothie tonight.

Keep the good info coming.

I told my alt doc today about ursolic acid, he looked at me like I was a genius.

No one has ever done that before.

Hugs,
Pete

Ps it's a great name Pete, it means rock but on can it's going to be remembered for nature. I hope.
Only nature heals in my opinion.

ditto
cancer.org server strikes again