Re: Wow -- waddya make of this?

[Guest guest]

-it is a study performed in laboratory with cell lines...

maybe some day another study will be performed with rats...

but a study with human beings is very improbable....unless

researchers combine sanguinarine with some (patented) chemical

toxins

karla

-- In , " jrrjim " <jim.mcelroy10@...> wrote:

>

> http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/148-

> ---------------------------------------------------

> Experimental and Molecular Therapeutics 5: Novel Agents 1

> Abstract #629

>

> Sanguinarine causes cell cycle arrest and apoptosis of human

> pancreatic cancinoma AsPC-1 and BxPC-3 cells

> Haseeb Ahsan, R. Reagan-Shaw, Jorien G. Breur and Nihal

Ahmad

> University of Wisconsin, Madison, WI

>

[Guest guest]

So what do you think of Sanguinarine (bloodroot) in general?

> >

> >

http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/148-

> > ---------------------------------------------------

> > Experimental and Molecular Therapeutics 5: Novel Agents 1

> > Abstract #629

> >

> > Sanguinarine causes cell cycle arrest and apoptosis of human

> > pancreatic cancinoma AsPC-1 and BxPC-3 cells

> > Haseeb Ahsan, R. Reagan-Shaw, Jorien G. Breur and Nihal

> Ahmad

> > University of Wisconsin, Madison, WI

> >

>

[Guest guest]

" jrrjim " <jim.mcelroy10> wrote:

> So what do you think of Sanguinarine (bloodroot) in general?

>

-Theoretically, it could be promising...but what happens

in real patients?

If you are experimenting with it, good luck

karla

Sanguinarine causes DNA damage and p53-independent cell death in

human colon cancer cell lines.

Matkar SS, Wrischnik LA, Hellmann-Blumberg U.

Department of Chemistry, University of the Pacific, Stockton, CA

95211, USA.

The benzophenanthridine alkaloid sanguinarine has antimicrobial and

possibly anticancer properties but it is not clear to what extent

these activities involve DNA damage. Thus, we studied its ability to

cause DNA single and double strand breaks, as well as increased

levels of 8-oxodeoxyguanosine, in human colon cancer cells and found

DNA damage consistent with oxidation. Since the tumor suppressor p53

is frequently involved in inducing apoptosis following DNA damage we

investigated the effect of sanguinarine in wild type, p53-mutant and

p53-null colon cancer cell lines. We found them to be equally

sensitive to this plant compound, indicating that cell death is not

mediated by p53 in this case. In addition, our observation that

apoptosis induced by sanguinarine is initiated very rapidly raised

the question whether there is enough time for cellular signaling in

response to DNA damage. Moreover, the abundance of double strand

breaks is not consistent with only oxidative damage to DNA. We

conclude that the majority of DNA double strand breaks in

sanguinarine-treated cells are likely the result, rather than the

cause, of apoptotic cell death and that apoptosis induced by

sanguinarine is independent of p53 and most likely independent of DNA

damage.

PMID: 18

Sanguinarine-induced apoptosis is associated with an early and severe

cellular glutathione depletion.

Debiton E, Madelmont JC, Legault J, Barthomeuf C.

UMR-INSERM U-484, Rue Montalembert, BP 184, 63005, Clermont-Ferrand,

France.

PURPOSE: The quaternary benzophenanthridine alkaloid sanguinarine

exhibits a broad range of activity, including cytotoxicity against

various human tumour and normal cell lines. Here, we examined its

potency as an anticancer drug. METHODS: The differential cytotoxicity

against cancer versus normal cells was assessed in vitro by two

fluorimetric assays (RRT and Hoechst 33342 dye DNA assays,

respectively) in a panel of human solid cancer cell lines and a human

fibroblast primary culture. The ability to induce apoptosis was

demonstrated in PC3 human prostatic adenocarcinoma cells by analysis

of morphological changes, internucleosomal DNA fragmentation,

cellular poly(ADP-ribose) polymerase cleavage and caspase 3/7

activation. Production of reactive oxygen species was evaluated by

the 2',7'-dichlorofluorescin diacetate assay. Depletion of cellular

glutathione content was assessed with the monochlorobimane assay.

RESULTS: Sanguinarine markedly inhibited the growth of all tested

cells (IC(50) 0.9-3.3 microM) without differential cytotoxicity

against normal versus cancer cells. In PC3 cells, continuous

treatment with 5 microM sanguinarine induced an early (within 10 min)

cellular reduced glutathione depletion insensitive to dithiothreitol

or N-acetylcysteine treatment, followed by a caspase 3/7-dependent

apoptotic response within 2 h. Complementary assays suggested that

the glutathione depletion was initiated by direct reactivity of

sanguinarine with reduced glutathione. CONCLUSIONS: Taken together,

these results show that (1) sanguinarine exhibits no specificity for

cancer cells, and (2) its strong cytotoxicity is probably due to a

rapid apoptotic response induced by an early and severe glutathione-

depleting effect. They also suggest that the clinical usefulness of

this alkaloid as an anticancer drug is limited.

" minolfa " <rapaccini.carlo@> wrote:

> > -it is a study performed in laboratory with cell lines...

> > maybe some day another study will be performed with rats...

> > but a study with human beings is very improbable....unless

> > researchers combine sanguinarine with some (patented) chemical

> > toxins. karla

> >

" jrrjim " <jim.mcelroy10@> wrote:

http://www.aacrmeetingabstracts.org/cgi/content/abstract/2005/1/148-