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

BMC Cancer
Wenyi GuChengzhong Yu

Abstract

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. 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. 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 signalin...Continue Reading

References

Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·K YamauchiJ E Pessin
Apr 1, 1996·Current Opinion in Cell Biology·M Streuli
Dec 16, 1998·The Journal of Biological Chemistry·S J HaqueB R Williams
Jan 10, 2002·The Journal of Biological Chemistry·Jess M CunnickJie Wu
Jan 29, 2002·Cellular Signalling·Helen WheadonMelanie J Welham
Mar 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Muhammad Al-HajjMichael F Clarke
May 21, 2003·Genes & Development·Gabriela DontuMax S Wicha
Jan 19, 2008·Nature·Tobias SchattonMarkus H Frank
Apr 19, 2008·Cell Death and Differentiation·X-D Zhou, Y M Agazie
Sep 12, 2008·Nature Reviews. Cancer·Jane E Visvader, Geoffrey J Lindeman
Mar 6, 2009·The Journal of Biological Chemistry·Xiangdong Zhou, Yehenew M Agazie
Oct 17, 2009·Cancer Investigation·Eiichi NakaiKeiji Shimizu
Jul 10, 2010·International Journal of Cancer. Journal International Du Cancer·Sze Ue LukMing-Tat Ling
Dec 29, 2010·PloS One·Chizuko TsurumiGabriele Niedermann
May 11, 2012·Planta medica·Thomas Efferth
May 19, 2012·Current Drug Targets·Joseph BurnettDuxin Sun
Jul 4, 2012·Cancer Metastasis Reviews·Darshni ViraEri S Srivatsan
Aug 3, 2012·Nature·Gregory DriessensCédric Blanpain
May 3, 2013·The Journal of Clinical Investigation·Taro Yamashita, Xin Wei Wang

❮ Previous
Next ❯

Citations

Aug 2, 2018·Journal of Cellular Physiology·Marina Montagnani MarelliPatrizia Limonta
Jan 18, 2019·Recent Patents on Anti-cancer Drug Discovery·Fabrizio FontanaPatrizia Limonta
Apr 25, 2019·European Journal of Nutrition·Constantina ConstantinouDimitrios Kanakis
Jul 28, 2020·International Journal of Molecular Sciences·Han-A ParkYonghyun Kim

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
PCR
ESR
xenograft

Software Mentioned

GraphPad Prism

Related Concepts

Related Feeds

Carcinoma, Ductal

Ductal carcinoma is a malignant neoplasm involving the ductal systems of any of a number of organs, such as the mammary glands, pancreas, prostate or lacrimal gland. Discover the latest research on ductal carcinoma here.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease with approximately 20,000 cases per year in the United States. AML also accounts for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. Here is the latest research on this disease.

Breast Invasive Carcinoma (Keystone)

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Cancer Stem Cells in Glioblastoma

Glioblastoma is the most common and aggressive type of brain tumor. It contains a population of tumor initiating stem cell-like cells known as cancer stem cells. Investigations are ongoing into these cancer stem cells found in these solid tumors which are highly resistance to treatment. Here is the latest research on cancer stem cells in glioblastoma.

Breast Invasive Carcinoma

Invasive breast cancers indicate a spread into breast tissues and lymph nodes. Here are the latest discoveries pertaining to breast invasive carcinomas.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Breast Cancer: Therapeutic Approaches

Several different therapeutic approaches are used to treat breast cancer. These include chemotherapy, hormonal therapy, targeted therapy, and Immunotherapy. Discover the latest research on breast cancer therapeutic approaches here.

AML: Role of LSD1 by CRISPR (Keystone)

Find the latest rersearrch on the ability of CRISPR-Cas9 mutagenesis to profile the interactions between lysine-specific histone demethylase 1 (LSD1) and chemical inhibitors in the context of acute myeloid leukemia (AML) here.

Breast Cancer: Risk Factors

Breast cancer is a multifactorial disease that is influenced by both environmental and genetic factors. Discover the latest research on the environmental and genetic risk factors for breast cancer here.