Journal
ENDOCRINE-RELATED CANCER
Volume 22, Issue 4, Pages 577-591Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-15-0192
Keywords
glutaminase; glutamate dehydrogenase; ovarian cancer; mTOR/S6; siRNA
Categories
Funding
- NIH/NCI [1K23CA143154-01A1]
- Steelman fund
- NATIONAL CANCER INSTITUTE [K23CA143154] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Glutamine is one of the main nutrients used by tumor cells for biosynthesis. Therefore, targeted inhibition of glutamine metabolism may have anti-tumorigenic implications. In the present study, we aimed to evaluate the effects of glutamine on ovarian cancer cell growth. Three ovarian cancer cell lines, HEY, SKOV3, and IGROV-1, were assayed for glutamine dependence by analyzing cytotoxicity, cell cycle progression, apoptosis, cell stress, and glucose/glutamine metabolism. Our results revealed that administration of glutamine increased cell proliferation in all three ovarian cancer cell lines in a dose dependent manner. Depletion of glutamine induced reactive oxygen species and expression of endoplasmic reticulum stress proteins. In addition, glutamine increased the activity of glutaminase (GLS) and glutamate dehydrogenase (GDH) by modulating the mTOR/S6 and MAPK pathways. Inhibition of mTOR activity by rapamycin or blocking S6 expression by siRNA inhibited GDH and GLS activity, leading to a decrease in glutamine-induced cell proliferation. These studies suggest that targeting glutamine metabolism may be a promising therapeutic strategy in the treatment of ovarian cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available