“Disruption of the molecular clock severely affects lipid metabolism in a hepatocellular carcinoma cell model”

Monjes, Natalia M.; Wagner, Paula M.; Guido, Mario E.

doi:10.1016/j.jbc.2022.102551

Cited by 9 publications

(9 citation statements)

References 59 publications

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“…These results strongly indicate a significant effect of the GSK-3 inhibitor on LD levels at the times evaluated showing the highest impact at 6 h after synchronization compared to control cultures. The differences observed in LD parameters after GSK-3 inhibition could result from, at least in part, the tight regulation by the circadian clock as previously shown for the LD content (Monjes et al 2022 ) and other metabolic parameters in different cancer cells (Wagner et al 2018 , 2019 ) (reviewed in (Guido et al 2022 )) as well as the differential response to pharmacological modulation of clock proteins.…”

Section: Resultsmentioning

confidence: 62%

Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology

Wagner,

Fornasier,

Guido

2024

Cell Mol Neurobiol

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The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12–15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase 1 ε/δ (CK1ε/δ) with specific inhibitors (CHIR99021 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99021-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99021 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects GBM cell biology.

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Section: Resultsmentioning

confidence: 62%

Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology

Wagner,

Fornasier,

Guido

2024

Cell Mol Neurobiol

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“…After DEX pulse (t 0 ), cells were collected at 6 and 18 h after synchronization. For lipid droplet (LD) staining, cells were fixed with 4% paraformaldehyde for 15 minutes and washed twice with PBS according to [87, 88]. Then, coverslips were incubated with Bodipy (Sigma cat#790389, maximum excitation/emission wavelength: 493/503 nm) at a final concentration of 2 μM for 30 minutes protected from light.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology

Wagner,

Guido

2023

Preprint

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The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12-15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase ε/δ (CK1ε/δ) with specific inhibitors (CHIR99022 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption afterPer2 knockdown expression in GBM-derived cells. CHIR99022-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition as compared with control cells. The combined treatment of CHIR99022 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone.Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects glioblastoma cell biology.

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“…After DEX pulse (t 0 ), cells were collected at 6 and 18 h after synchronization. For lipid droplet (LD) staining, cells were xed with 4% paraformaldehyde for 15 minutes and washed twice with PBS according to (Monjes et al 2022). Then, coverslips were incubated with Bodipy (Sigma cat#790389, maximum excitation/emission wavelength: 493/503 nm) at a nal concentration of 2 µM for 30 minutes protected from light.…”

Section: Immunocytochemistrymentioning

confidence: 99%

Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology

Wagner,

Guido

2024

Preprint

View full text Add to dashboard Cite

The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12–15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase ε/δ (CK1ε/δ) with specific inhibitors (CHIR99022 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99022-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99022 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects glioblastoma cell biology.

show abstract

“Disruption of the molecular clock severely affects lipid metabolism in a hepatocellular carcinoma cell model”

Cited by 9 publications

References 59 publications

Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology

Pharmacological Modulation of the Cytosolic Oscillator Affects Glioblastoma Cell Biology

Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology

Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology

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