Glutaminase inhibitor compound 968 inhibits cell proliferation and sensitizes paclitaxel in ovarian cancer

Objective: Our overall goal was to investigate the anti-tumor activity of the glutaminase 1 (GLS1) Inhibitor compound 968 in ovarian cancer cells. The human ovarian cancer cell lines, HEY, SKOV3 and IGROV-1 were used. Cell proliferation was assessed by MTT assay after treatment with compound 968. Cell cycle progression and Annexin V expression were evaluated using Cellometer. Western blotting was performed to determine changes in GLS1, cellular stress and cell cycle checkpoints. Reactive oxygen species (ROS) and glutamate dehydrogenase (GDH) activity were assessed by ELISA assay. Compound 968 significantly inhibited cell proliferation and the expression of GLS1 in a dose-dependent manner in all three ovarian cancer cell lines. Compound 968 induced G1 phase cell cycle arrest and apoptosis. Treatment with compound 968 increased ROS levels and induced the protein expression of calnexin, binding immunoglobulin protein (BiP) and protein kinase RNA-like endoplasmic reticulum kinase (PERK). Deprivation of glutamine increased the sensitivity of cells to paclitaxel, and compound 968 sensitized cells to the anti-proliferative effects of paclitaxel. Compound 968 inhibited cell growth in ovarian cancer cells through induction of G1 phase cell cycle arrest, apoptosis and cellular stress, suggesting that targeting GLS1 provide a novel therapeutic strategy for ovarian cancer

Testing the equivalence principle via the shadow of black holes

Funding: H.Z. acknowledges support from the USTC fellowship for international visiting professors and from Shanghai Astronomical Observatory. This work is sup- ported in part by the NSFC (No. 11722327, No. 11653002, No. 11961131007, No. 11725312, No. 11421303), by the CAST (No. 2016QNRC001), by the National Youth Talents Program of China, and by the Fundamental Research Funds for Central Universities. The work of D.A.E. is supported in part by the Foundational Questions Institute.We study the equivalence principle, regarded as the cornerstone of general relativity, by analyzing the deformation observable of black hole shadows. Such deformation can arise from new physics and may be expressed as a phenomenological violation of the equivalence principle. Specifically, we assume that there is an additional background vector field that couples to the photons around the supermassive black hole. This type of coupling yields impact on the way the system depends on initial conditions and affects the black hole shadow at different wavelengths by a different amount, and therefore observations of the shadow in different wavelengths could constrain such couplings. This can be tested by future multiband observations. Adopting a specific form of the vector field, we obtain constraints on model parameters from Event Horizon Telescope observations and measurements of gas/stellar orbits.Publisher PDFPeer reviewe

Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway

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

The role of vitamin D in ovarian cancer: epidemiology, molecular mechanism and prevention

Abstract Vitamin D is a fat-soluble prohormone best known for its role in maintaining calcium homeostasis. Large numbers of epidemiological studies have shown that vitamin D plays an important role in cancer prevention by regulating cellular proliferation and metabolism. Studies of the cellular mechanism of vitamin D in ovarian cancer strongly suggest that it exhibits protective and antitumorigenic activities through genomic and nongenomic signal transduction pathways. These results indicate that vitamin D deficiency results in an increase in the risk of developing ovarian cancer and that vitamin supplements may potentially be an efficient way of preventing cancer. Consequently, this review describes the epidemiology, molecular mechanism and evidence linking vitamin D deficiency to ovarian cancer

Glutamine promotes ovarian cancer cell proliferation through the mTOR/S6 pathway

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