Gamma tocotrienol targets tyrosine phosphatase SHP2 in mammospheres resulting in cell death through RAS/ERK pathway

Gu, Wenyi, Prasadam, Indira, Yu, Meihua, Zhang, Fengxia, Ling, Patrick, Xiao, Yin and Yu, Chengzhong (2015) Gamma tocotrienol targets tyrosine phosphatase SHP2 in mammospheres resulting in cell death through RAS/ERK pathway. BMC Cancer, 15 1: 1-11. doi:10.1186/s12885-015-1614-1


Author Gu, Wenyi
Prasadam, Indira
Yu, Meihua
Zhang, Fengxia
Ling, Patrick
Xiao, Yin
Yu, Chengzhong
Title Gamma tocotrienol targets tyrosine phosphatase SHP2 in mammospheres resulting in cell death through RAS/ERK pathway
Journal name BMC Cancer   Check publisher's open access policy
ISSN 1471-2407
Publication date 2015-08-28
Year available 2015
Sub-type Article (original research)
DOI 10.1186/s12885-015-1614-1
Open Access Status DOI
Volume 15
Issue 1
Start page 1
End page 11
Total pages 11
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Subject 2730 Oncology
1311 Genetics
1306 Cancer Research
Abstract Background: There 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.
Formatted abstract
Background:  There 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.

Methods:  We 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.

Results:  We 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.

Conclusions:  SHP1 and SHP2 are potential therapeutic targets for breast CSCs and gamma-T3 is a promising natural drug for future breast cancer therapy.
Keyword Mammospheres
Gamma tocotrienol
Tyrosine phosphatase SHP2
Cell death
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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