Feverfew Extract Preferentially Attacks CLL Cells

[Guest guest]

[i have been in contact with a group of researchers who are working

with this substance on various leukemias, including CLL. Work

continues on isolating and enhancing the active ingredient,

parthenolide. See note below regarding the poor availability of

parthenolide from herbal feverfew.]

Leukemia. 2006 Apr 20; [Epub ahead of print]

The sesquiterpene lactone parthenolide* induces selective apoptosis

of B-chronic lymphocytic leukemia cells in vitro.

Steele AJ, DT, Ganeshaguru K, Duke VM, Yogashangary BC, North

JM, Lowdell MW, Kottaridis PD, Mehta AB, Prentice AG, Hoffbrand AV,

Wickremasinghe RG.

1Department of Hematology, Royal Free and University College Medical

School, London, UK.

We have studied the in vitro actions of the sesquiterpene lactone

parthenolide (PTL) on cells isolated from patients with chronic

lymphocytic leukemia (CLL).

Dye reduction viability assays showed that the median LD(50)** for

PTL was 6.2 muM (n=78). Fifteen of these isolates were relatively

resistant to the conventional agent chlorambucil but retained

sensitivity to PTL. Brief exposures to PTL (1-3 h) were sufficient to

induce caspase activation and commitment to cell death.

Chronic lymphocytic leukemia cells were more sensitive towards PTL

than were normal T lymphocytes or CD34(+) haematopoietic progenitor

cells.

The mechanism of cell killing was via PTL-induced generation of

reactive oxygen species, resulting in turn in a proapoptotic Bax

conformational change, release of mitochondrial cytochrome c and

caspase activation. Parthenolide also decreased nuclear levels of the

anti-apoptotic transcription factor nuclear factor-kappa B and

diminished phosphorylation of its negative regulator IkappaB. Killing

of CLL cells by PTL was apparently independent of p53 induction.

This is the first report showing the relative selectivity of PTL

towards CLL cells. The data here warrant further investigation of

this class of natural product as potential therapeutic agents for CLL.

Leukemia advance online publication, 20 April 2006;

doi:10.1038/sj.leu.2404230.

PMID: 16628188 [PubMed - as supplied by publisher]

*The component of feverfew that shows the most anti-tumor activity.

Unfortunately, the bioavailability of parthenolide from feverfew is

very, very low. Using the herb will not deliver any appreciable

amounts of parthenolide to the body.

**The dose that kills 50% of the cells in a sample.