CSN Login
Members Online: 2

You are here

Drug kills cancer stem cells

smokeyjoe
Posts: 1428
Joined: Feb 2011

McMaster University researchers discover drug destroys human cancer stem cells but not healthy onesPublished: May 24, 2012

Mick Bhatia, scientific director of McMaster's Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.

"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells; by changing them into cells that are non-cancerous," said Mick Bhatia, the principal investigator for the study and scientific director of McMaster's Stem Cell and Cancer Research Institute (SCC-RI) in the Michael G. DeGroote School of Medicine.

Unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells.

The research, published today in the science journal CELL, holds the promise of a new strategy and discovery pipeline for the development of anticancer drugs in the treatment of various cancers. The research team has identified another dozen drugs that have good potential for the same response.

For 15 years, some researchers have believed stem cells are the source of many cancers. In 1997, Canadian researchers first identified cancer stem cells in certain types of leukemia. Cancer stem cells have since been identified in blood, breast, brain, lung, gastrointestinal, prostate and ovarian cancer.

To test more than a dozen different compounds, McMaster researchers pioneered a fully automated robotic system to identify several drugs, including thioridazine.

"Now we can test thousands of compounds, eventually defining a candidate drug that has little effect on normal stem cells but kills the cells that start the tumor," said Bhatia.

The next step is to test thioridazine in clinical trials, focusing on patients with acute myeloid leukemia whose disease has relapsed after chemotherapy. Bhatia wants to find out if the drug can put their cancer into remission, and by targeting the root of the cancer (cancer stem cells) prevent the cancer from coming back. Researchers at McMaster have already designed how these trials would be done.

Bhatia's team found thioridazine works through the dopamine receptor on the surface of the cancer cells in both leukemia and breast cancer patients. This means it may be possible to use it as a biomarker that would allow early detection and treatment of breast cancer and early signs of leukemia progression, he said. The research team's next step is to investigate the effectiveness of the drug in other types of cancer. In addition, the team will explore several drugs identified along with thioridazine. In the future, thousands of other compounds will be analyzed with McMaster robotic stem cell screening system in partnership with collaborations that include academic groups as well as industry.

"The goal for all of the partners is the same — to find unique drugs to change the way we tackle and treat cancer," he said.

pete43lost_at_sea's picture
pete43lost_at_sea
Posts: 3908
Joined: Nov 2010

i will dream i have been injected and any of those little metastatis forming stem cells will be killed. its about time they solved this pain in the arse problem. i could stop being forest gump then and get back to diving with sharks. something much safer than playing with colorectal cancer.

just great news, such fabulous news. looks of hope everywhere, we don't have to look to far, just at each other.

thanks smokeyjoe.

hugs,
pete

ps sweet dreams from australia

Lovekitties's picture
Lovekitties
Posts: 3304
Joined: Jan 2010

thioridazine is an old antipsychotic drug.

It was not recommended for patients who had in the past or currently had breast cancer.

Of course as an antipsychotic it was prescribed for a long duration. From what I read elsewhere, they are looking at a 30 day period for using it in treating cancer.

Hoping that if it does show real promise that the known side effects from prolonged use do not show up in the short term usage. Some were pretty severe or lethal.

John23's picture
John23
Posts: 2140
Joined: Jan 2007

smokeyjoe -

"For all patients:

Thioridazine can cause a serious type of irregular heartbeat that
may cause sudden death. There are other medications that can be
used to treat your condition that are less likely to cause this
life-threatening side effect. "

From: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682119.html

"Your mileage may vary"

Best wishes,

John

dmj101's picture
dmj101
Posts: 527
Joined: Nov 2011

Really. this is a really dangerous drug.. It is a anti-pyschotic, with many lawsuits against it for the the leathal side effects it has.
Now I realize given the consequences of not trying it may be just as leathal.. I am not sure .. a doc would have to really sell it to me..

smokeyjoe
Posts: 1428
Joined: Feb 2011

Yeah, seems everything has risks, side effects :( Look at the side effects of Avastin, yet it works wonderfully for a lot of people on it for a great length of time. It will be interesting to see how long you'd have to take this drug for it to have an effect on the cancer cells.

steved
Posts: 835
Joined: Apr 2004

This is an antipsychotic I prescribed for years as a psychiatrist but was withdrawn a few years back because of teh accumulating evidence of a link to arrythmias in the heart. My sense was it was very safe for the vast majority and was often used for anxious people who weren't psychotic for its generally calming properties. We now have safer antipsychotics and its use in psychiatry isn't justified but in a field like oncology there is a greater tolerance of potential side effects if drugs are found to be effective because of teh severity of the illnesses that are being treated.

I am not aware of any particular link between dopamine and colorectal cancer however (it is a dopamine blocking drug) so is unlikely to be useful for us but in breast cancer and leaukemias it may have a role.

steve

dmj101's picture
dmj101
Posts: 527
Joined: Nov 2011

What I find really scary about something like this is the attitude.. well it may kill others but if they already have cancer what a few more life altering and leathal opportunities to ruin those peoples life.. Sorry I may be sinical. and I even work in the medical testing business.. but I am really not willing to suffer any further than I really have too.. especially now that I have experienced the effects of Oxaliplatin.. this is no joke.. for the sake of one disease who cares if the person can't walk.. take care of themselves anymore.. is that really humane.. I mean.. we would put our dog to sleep before we'd do that to them but we are will to lame people with cancer... comm''on.. really
This makes me so angry..

John23's picture
John23
Posts: 2140
Joined: Jan 2007

Re:
"well it may kill others but if they already have cancer what a few
more life altering and leathal opportunities to ruin those peoples life.. "

That's what our TCM doc has always said!

No-one can predict our mortality; no-one can determine when
our life will end (unless they're the ones that are going to end it).

So why does anyone take medications that will do harm, thinking
that they are going to die anyway?

Anyone that worries about taking any medication or food product,
or tobacco product.... or holding a cellphone too close to one's head
during a call, should realize that the very same chemicals that are
being taken to resolve cancer, are all carcinogenic and can cause death.

We have to weigh the good vs the bad, and -not- allow the fear of
"not taking a conventional remedy" to rule us.

If our instincts tell us to avoid something, it's usually best to follow
those instincts. Looking back after taking damaging chemicals and
wishing we took a different route, is worse than not having taken
that route at all.

We all have the benefit of having received the gift of self-preservation;
it's the gift of an inner intuition that tells us right from wrong.

We really should listen to it more often!

Best of health to all,

John

dmj101's picture
dmj101
Posts: 527
Joined: Nov 2011

Thanks John,
I am still angry.. I don't know the solution..
I don't use a TCM but they have a point.. They have been around thousands of years using their same practices for centuries.. they can't be wrong..
Don't doctors take an oath to DO NO HARM....
I mean I still believe in western and modern medicine but I use my gut to decide what I do and don't do .. I wish more did. and more spoke out about these horrible practices.

smokeyjoe
Posts: 1428
Joined: Feb 2011

I found this on line pubmed...Abstract
PURPOSE: Because neurotransmitter dopamine inhibits vascular permeability factor/vascular endothelial growth factor (VEGF)-induced angiogenesis and as anti-VEGF agents act synergistically with anticancer drugs, we therefore investigated whether dopamine can increase the efficacies of these drugs.

EXPERIMENTAL DESIGN: The effect of dopamine was investigated in human breast cancer-(MCF-7) and colon (HT29) cancer-bearing mice. Experimental groups received either dopamine or doxorubicin or dopamine plus doxorubicin in MCF-7 tumor-bearing mice, and either dopamine or 5-fluorouracil or dopamine plus 5-fluorouracil in HT29-bearing mice. Thereafter, tumor growth, angiogenesis, tumor cell apoptosis, life span, and the effect of dopamine on the growth and survival of tumor cells in vitro were determined. Finally, the effects of dopamine on tumor vascular permeability; on VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation; and also on the proliferation and migration of tumor endothelial cells were investigated.

RESULTS: Dopamine, in combination with anticancer drugs, significantly inhibited tumor growth and increased the life span when compared with treatment with dopamine or anticancer drugs alone. Dopamine had no direct effects on the growth and survival of tumor cells. The antiangiogenic action of dopamine was mediated by inhibiting proliferation and migration of tumor endothelial cells through suppression of VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation.

CONCLUSION: Our study shows that dopamine significantly enhances the efficacies of commonly used anticancer drugs and also indicates that an inexpensive drug like dopamine, which is being extensively used in the clinics, might have a role as an antiangiogenic agent for the treatment of breast and colon cancer.

Lovekitties's picture
Lovekitties
Posts: 3304
Joined: Jan 2010

Do you have a date for this paper? Where was the study done?

Thanks

smokeyjoe
Posts: 1428
Joined: Feb 2011

Hey Marie, I'll see if I can find it again....if my memory serves me right it was like in 2008 from what I read...I'm surprised when I attached it that it didn't have that.....but I found it interesting as it seemed to be totally opposite effect that they are stating in the McMaster studies....I shall search what I did and repost for you....I was hoping our resident psych. would have some more comments...Expand+Clinical Cancer Researchclincancerres.aacrjournals.orgdoi: 10.1158/1078-0432.CCR-07-1778 Clin Cancer Res April 15, 2008 14; 2502
Dopamine Increases the Efficacy of Anticancer Drugs in Breast and Colon Cancer Preclinical Models
Chandrani Sarkar1,3, Debanjan Chakroborty1,3, Uttio Roy Chowdhury1, Partha Sarathi Dasgupta1 and Sujit Basu2,3,4
+ Author Affiliations

Authors' Affiliations:1Signal Transduction and Biogenic Amines Laboratory and 2Department of Medical Oncology, Chittaranjan National Cancer Institute, Kolkata, India; and 3Department of Biochemistry and Molecular Biology and 4Mayo Clinic Cancer Center, Mayo Clinic, Rochester, Minnesota
Requests for reprints:
Partha Sarathi Dasgupta, Signal Transduction and Biogenic Amines Laboratory, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata 700026, India. Phone: 91-33-24765101, ext. 324; E-mail: partha42002@yahoo.com or Sujit Basu, Department of Biochemistry and Molecular Biology and Cancer Center, Mayo Clinic, Gugg 1793, 200 First Street Southwest, Rochester, MN 55905. Phone: 507-284-1344; E-mail: basu.sujit@mayo.edu.
Abstract
Purpose: Because neurotransmitter dopamine inhibits vascular permeability factor/vascular endothelial growth factor (VEGF)–induced angiogenesis and as anti-VEGF agents act synergistically with anticancer drugs, we therefore investigated whether dopamine can increase the efficacies of these drugs.

Experimental Design: The effect of dopamine was investigated in human breast cancer–(MCF-7) and colon (HT29) cancer–bearing mice. Experimental groups received either dopamine or doxorubicin or dopamine plus doxorubicin in MCF-7 tumor-bearing mice, and either dopamine or 5-fluorouracil or dopamine plus 5-fluorouracil in HT29-bearing mice. Thereafter, tumor growth, angiogenesis, tumor cell apoptosis, life span, and the effect of dopamine on the growth and survival of tumor cells in vitro were determined. Finally, the effects of dopamine on tumor vascular permeability; on VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation; and also on the proliferation and migration of tumor endothelial cells were investigated.

Results: Dopamine, in combination with anticancer drugs, significantly inhibited tumor growth and increased the life span when compared with treatment with dopamine or anticancer drugs alone. Dopamine had no direct effects on the growth and survival of tumor cells. The antiangiogenic action of dopamine was mediated by inhibiting proliferation and migration of tumor endothelial cells through suppression of VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation. K...Marie here you go....hope you can make sense of it....I'm blonde, that's my excuse....

Lovekitties's picture
Lovekitties
Posts: 3304
Joined: Jan 2010

Well I may not be blond, but I feel a bit overwhelmed with all the lingo.

Here is my take on what it says...one of the authors is/was affiliated with Mayo Clinic (the only place I recognize)...it seems that in their testing dopamine, when used in conjunction with 5-FU (which I recognize as a colorectal chemo)in mice with colon adenocarcinoma cells, shows that it 'significantly inhibited tumor growth and increased the life span'.

This made me go looking for the specifics and here is a more recent site from a study at Ohio State University Comprehensive Cancer Center published Dec. 2011.

http://www.eurekalert.org/pub_releases/2011-12/osum-ans120111.php

The important part for we colorectal patients is at the bottom:

•Subcutaneous human colon tumors in mice treated with dopamine and the chemotherapeutic drug 5-fluorouracil (5-FU) accumulated twice the amount of 5-FU as tumors in mice treated with the drug only.

•Subcutaneous human colon tumors in mice treated with both dopamine and 5-FU were less than one-third the size of tumors in mice treated with 5-FU only.

Good info and may be worth passing on to your onc for review if you are on or starting 5-FU.

Thanks for sharing.

Hugs,

Marie who loves kitties

John23's picture
John23
Posts: 2140
Joined: Jan 2007

But Steved made a great point!

Re:
"I am not aware of any particular link between dopamine and
colorectal cancer however (it is a dopamine blocking drug) so is
unlikely to be useful for us but in breast cancer and leaukemias
it may have a role."

Thioridazine blocks dopamine, and doing that does not help
chemo fight cancer.

When any company pays an institution to do a "study", that company
owns that report. They are legally free to reveal or not reveal anything
in that study. They can add to that report, change it, or fabricate facts
as they see fit. It's called "forward looking statements" that are designed
to encourage would-be investors to invest in their company.

Caveat Emptor....

(and thank you Steved, for bringing Thioridazine's dopamine factor
into view!)

Best of health to all!

John

steved
Posts: 835
Joined: Apr 2004

The role of dopamine (DA) and cancer in general is complex and different in different cancers. The link to breast cancer is the longest known where if we use DA blockers (like thioridazine) we tend to increase a hormone level called prolactin (the one stimulated at birth to trigger lactation) and raised prolactin may increase the risk of breast cancer- this is an indirect effect of DA blockade.

In some of the literature above they are finding that dopamine has a role in maintaining the blood vessel structure in normal tissue. In cancer tissues blood vessels are often chaotic and leaky and this is one reason why chemo drugs don't penetrate into tumours as well. The reason for the leakiness may be that these vessels don't have as many dopamine receptors in them. Hence treating with dopamine may improve the blood vessels and allow chemo to penetrate the tumour better. This is the theory behind using dopamine and this is true in mice with colon cancer (not tested in humans).

The separate issue of using dopamine blockers seems more specific to those cancers that are based on stem cells. It is unknown whether stem cells are relevant in all cancers- certainly colorectal isn't felt to be highly likely to be due to wonky stem cells. Some specific cancers like leukemia and lymphomas are felt to be be caused by wonkey stem cells. In these cells using dopamine blockers may covert the wonky stem cells to normal cells.

Complex and all very early- only animal studies which generally means it is some years off use in humans. They may start some human studies of using dopamine but it wouldn't be recommended outside of these studies as it isn't sufficiently proven to be of use. One of the strengths of conventional medicine is that nothing makes it into general use without good scientific testing in animals and humans - interestingly this isn't true of complementary meds which are often untested as to their efectiveness and their toxicity.

Hope this is useful,
steve

John23's picture
John23
Posts: 2140
Joined: Jan 2007

Re:
"The separate issue of using dopamine blockers seems more
specific to those cancers that are based on stem cells. It is unknown
whether stem cells are relevant in all cancers"

Or relevant to cancer at all?

It's the belief of a growing number of oncologists, that knowing
the basic way a cancer cell cell manages to begin it's life, is what
is being overlooked as the main target of attack.

Something as simple as an amoeba; something as simple as a
one cell life-form, surviving by the fermentation process alone,
is being attacked by methods more complex than the cell's basic
structure, with all methods failing eventually.

We're trying to smash a pebble using nuclear bombs.

"Sometimes the wrong road can look so right when we forget
where we were headed."

Thanks, and best of health to you!

John

Subscribe to Comments for "Drug kills cancer stem cells"