Telomerase, inflammation/IL-8....let's keep adding to the list of cancer stem cell strategies.
Hmmm..
However it does it,
Milk thistle seems to reduce a proposed cancer stem cell marker:
Am J Transl Res. 2009 Jan 1;1(1):80-6.
Silibinin suppresses CD44 expression in prostate cancer cells.
Handorean AM,
Yang K,
Robbins EW,
Flaig TW,
Iczkowski KA.
Prostate cancer (PCa), like most human cancers, features dysregulated CD44 expression. Expression of CD44 standard (CD44s), present in benign epithelium, is lost in PCa while pro-invasive splice variant isoform CD44v7-10 is overexpressed. The role of CD44 in silibinin's anti-growth effects was uncertain. To assess silibinin's effects on CD44 promoter activity, PC-3M PCa cells were transfected with luciferase-CD44 promoter construct 24 h prior to 25-200 muM silibinin treatment for 48 h. Also, cells' expression of CD44 RNA (by qRT-PCR) and protein (Western blot analysis) was studied.
Silibinin was further tested preoperatively on a pilot cohort of 6 men with PCa compared with 7 matched placebo-treated men, with immunostaining for CD44v7-10 in their prostates. In PC-3M cells,
silibinin dose-dependently inhibited CD44 promoter activity up to 87%, caused a 90% inhibition of total CD44 and 70% decrease in CD44v7-10 RNA, and at the protein level, decreased total CD44 at 100-200 muM dose and decreased CD44v7-10 after 3 days. Silibinin decreased adhesion to hyaluronan and fibronectin. Silibinin at 100-200 muM inhibited Egr-1, a regulator of CD44 promoter activity. Men treated with silibinin did not differ in tissue CD44v7-10 expression. In conclusion, CD44 inhibition is one mechanism by which silibinin reduces PCa tumorigenicity.
PMID: 19966941 [PubMed - in process]
Proc Natl Acad Sci U S A. 2010 Feb 3. [Epub ahead of print]
Selective targeting of radiation-resistant tumor-initiating cells.
Zhang M,
Atkinson RL,
Rosen JM.
Department of Molecular and Cellular Biology and Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX 77030-3498.
Tumor-initiating cells (TICs) have been shown both experimentally and clinically to be resistant to radiation and chemotherapy, potentially resulting in residual disease that can lead to recurrence. In this study, we demonstrate that TICs isolated from p53 null mouse mammary tumors repair DNA damage following in vivo ionizing radiation more efficiently than the bulk of the tumor cells. Down-regulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was observed both in fluorescence activated cell sorting (FACS)-isolated TICs as compared to non-TICs and in TIC-enriched mammospheres as compared to primary tumor cells depleted of TICs. This effect was accompanied by increased Akt signaling, as well as by the direct activation of the canonical Wnt/beta-catenin signaling pathway specifically within the TIC subpopulation by phosphorylation of beta-catenin on serine 552. Using limiting dilution transplantation performed on p53 null tumor cells transduced with Wnt reporter lentivirus, we demonstrated that FACS sorting of cells expressing TOP-eGFP resulted in a marked enrichment for TICs. Furthermore, FACS analysis demonstrated that cells with active Wnt signaling overlapped with the TIC subpopulation characterized previously using cell surface markers. Finally,
pharmacological inhibition of the Akt pathway in both mammospheres and syngeneic mice bearing tumors was shown to inhibit canonical Wnt signaling as well as the repair of DNA damage selectively in TICs, sensitizing them to ionizing radiation treatment. Thus, these results suggest that pretreatment with Akt inhibitors before ionizing radiation treatment may be of potential therapeutic benefit to patients.
PMID: 20133717 [PubMed - as supplied by publisher]
Hybrid Mode
