Abstract
BackgroundThere is increasing evidence supporting the concept of cancer stem cells (CSCs), which are responsible for the initiation, growth and metastasis of tumors. CSCs are thus considered the target for future cancer therapies. To achieve this goal, identifying potential therapeutic targets for CSCs is essential.MethodsWe used a natural product of vitamin E, gamma tocotrienol (gamma-T3), to treat mammospheres and spheres from colon and cervical cancers. Western blotting and real-time RT-PCR were employed to identify the gene and protein targets of gamma-T3 in mammospheres.ResultsWe found that mammosphere growth was inhibited in a dose dependent manner, with total inhibition at high doses. Gamma-T3 also inhibited sphere growth in two other human epithelial cancers, colon and cervix. Our results suggested that both Src homology 2 domain-containing phosphatase 1 (SHP1) and 2 (SHP2) were affected by gamma-T3 which was accompanied by a decrease in K- and H-Ras gene expression and phosphorylated ERK protein levels in a dose dependent way. In contrast, expression of self-renewal genes TGF-beta and LIF, as well as ESR signal pathways were not affected by the treatment. These results suggest that gamma-T3 specifically targets SHP2 and the RAS/ERK signaling pathway.ConclusionsSHP1 and SHP2 are potential therapeutic targets for breast CSCs and gamma-T3 is a promising natural drug for future breast cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1614-1) contains supplementary material, which is available to authorized users.
Highlights
There is increasing evidence supporting the concept of cancer stem cells (CSCs), which are responsible for the initiation, growth and metastasis of tumors
We found that apart from the effect on Src homology domain-containing phosphatase 1 (SHP1), γ-T3 targeted SHP2 in breast cancer and that the γ-T3 inhibitory effect on CSC growth was through the RAS/ERK pathway
The mammosphere cells were separated and characterized for surface expression of CD44 and CD24, which are commonly considered as markers of breast cancer stem cells [2]
Summary
There is increasing evidence supporting the concept of cancer stem cells (CSCs), which are responsible for the initiation, growth and metastasis of tumors. The concept of cancer stem cells (CSCs) describes that tumors contain a small proportion of self-renewing and pluri-potent cells that are responsible for initiating and maintaining tumor growth [1]. This concept is well established in leukemia and has been reported in a few solid tumor types [2,3,4]. Recent studies further confirm that a specific cell population is responsible for the initiation and growth of solid tumors [5,6,7] These cells usually express high levels of multiple drug resistant gene (MDR1) [8] and ATP binding cassette (ABC) transporter [9] and are resistant to chemotherapy and considered as the major source of drug-resistance in tumors. They showed that the CD44 expression of the CSCs was decreased by
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
