Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling

Wu, Yukun; Li, Zhi-Zhang; Zhang, Lijuan; Liu, Guiyang

doi:10.12659/msm.919319

Cited by 5 publications

(5 citation statements)

References 42 publications

(45 reference statements)

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“…Tivantinib is a candidate anticancer agent for patients with hepatocellular carcinoma (HCC). A combination of Tivantinib, PI3K inhibitor LY294002 and mTOR inhibitor, rapamycin has been shown to largely inhibit the proliferation of glioblastoma cells [ 47 ]. Tivantinib was shown to inhibit GSK3α and to a lesser extent GSK3β in lung cancer cells [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Drug Repurposing in Dentistry: Towards Application of Small Molecules in Dentin Repair

Birjandi

Suzano

Sharpe

2020

IJMS

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One of the main goals of dentistry is the natural preservation of the tooth structure following damage. This is particularly implicated in deep dental cavities affecting dentin and pulp, where odontoblast survival is jeopardized. This activates pulp stem cells and differentiation of new odontoblast-like cells, accompanied by increased Wnt signaling. Our group has shown that delivery of small molecule inhibitors of GSK3 stimulates Wnt/β-catenin signaling in the tooth cavity with pulp exposure and results in effective promotion of dentin repair. Small molecules are a good therapeutic option due to their ability to pass across cell membranes and reach target. Here, we investigate a range of non-GSK3 target small molecules that are currently used for treatment of various medical conditions based on other kinase inhibitory properties. We analyzed the ability of these drugs to stimulate Wnt signaling activity by off-target inhibition of GSK3. Our results show that a c-Met inhibitor, has the ability to stimulate Wnt/β-catenin pathway in dental pulp cells in vitro at low concentrations. This work is an example of drug repurposing for dentistry and suggests a candidate drug to be tested in vivo for natural dentin repair. This approach bypasses the high level of economical and time investment that are usually required in novel drug discoveries.

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Section: Discussionmentioning

confidence: 99%

Drug Repurposing in Dentistry: Towards Application of Small Molecules in Dentin Repair

Birjandi

Suzano

Sharpe

2020

IJMS

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“…SKOV3 and OVCAR-3 cells were treated with 0, 2.5, 5, 10, 20, 40, 80 and 160 μM doses of ropivacaine (BioChemPartner, Shanghai, China) for 24 h. 15 SKOV3 and OVCAR-3 cells were treated with 40 μM ropivacaine and/or 5 mmol/l erastin (MedChemExpress, New Jersey, USA), 16 40 μM ropivacaine and/or 5 μM ferrostatin-1 (MedChemExpress) for 24 h. 17 SKOV3 cells were treated with 40 μM ropivacaine and/or 20 μM 740 Y-P (MedChemExpress) for 24 h. 18…”

Section: Methodsmentioning

confidence: 99%

“…SKOV3 and OVCAR-3 cells were treated with 0, 2.5, 5, 10, 20, 40, 80 and 160 μM doses of ropivacaine (Bio-ChemPartner, Shanghai, China) for 24 h. 15 SKOV3 and OVCAR-3 cells were treated with 40 μM ropivacaine and/or 5 mmol/l erastin (MedChemExpress, New Jersey, USA), 16 40 μM ropivacaine and/or 5 μM ferrostatin-1 (MedChe-mExpress) for 24 h. 17 SKOV3 cells were treated with 40 μM ropivacaine and/or 20 μM 740 Y-P (MedChemExpress) for 24 h. 18 Cell counting kit-8 (CCK-8) assay SKOV3 and OVCAR-3 cells (2 × 10 3 ) were inoculated in 96-well plates. After 24 h of culture, 10 μl CCK-8 solution (Beyotime, Shanghai, China) was added to each well and placed in an incubator for further culture for 1 h. Afterward, the 96-well plates were placed in a microplate reader (Thermo Fisher Scientific) and the absorbance (OD) at 450 nm was detected.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

Ropivacaine represses the ovarian cancer cell stemness and facilitates cell ferroptosis through inactivating the PI3K/AKT signaling pathway

Lü

Mao

et al. 2022

Hum Exp Toxicol

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Purpose Ovarian cancer is a malignant tumor in women all over the world. Ropivacaine is identified as a potential drug for the treatment of malignant tumors, but the role and mechanism of ropivacaine in ovarian cancer remains unknown. Materials and methods Ovarian cancer cells were treated with different doses of ropivacaine. The function of ropivacaine in ovarian cancer was assessed using Cell Counting Kit-8 assay, flow cytometry, sphere-formation assay, Western blot, Fe2+ level analysis, and immunofluorescence. Meanwhile, the mechanism of ropivacaine in ovarian cancer was investigated by multiple molecular experiments. The protective function of ropivacaine in ovarian cancer was further confirmed by in vivo assay. Results The functional research data indicated that the growth and stemness of ovarian cancer cells were restrained after ropivacaine treatment, while the ferroptosis in ovarian cancer cells was facilitated. The mechanism results confirmed that ropivacaine inactivated the PI3K/AKT signaling pathway in ovarian cancer cells. Furthermore, in vivo assay demonstrated that ropivacaine repressed the proliferation of ovarian cancer cells in vivo and had a protective function in ovarian cancer. Conclusion Ropivacaine restrained ovarian cancer cell stemness and accelerated cell ferroptosis by inactivating PI3K/AKT signaling pathway.

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“…When tested at high concentration (1 µmol/L) [82], tivantinib inhibited U251 and T98MG GBM cells proliferation and colony formation, while a lower concentration (0.1 µmol/L) did not affect cell proliferation. High concentration of tivantinib in combination with the PI3K inhibitor LY294002 and the mTOR inhibitor rapamycin, strongly inhibited GBM cell proliferation [82].…”

Section: Tivantinibmentioning

confidence: 96%

Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment

Frumento,

Grossi,

Falesiedi

et al. 2024

IJMS

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In the last decade, many small molecules, usually characterized by heterocyclic scaffolds, have been designed and synthesized as tyrosine kinase inhibitors (TKIs). Among them, several compounds have been tested at preclinical and clinical levels to treat glioblastoma multiforme (GBM). GBM is the most common and aggressive type of cancer originating in the brain and has an unfavorable prognosis, with a median survival of 15–16 months and a 5-year survival rate of 5%. Despite recent advances in treating GBM, it represents an incurable disease associated with treatment resistance and high recurrence rates. For these reasons, there is an urgent need for the development of new pharmacological agents to fight this malignancy. In this review, we reported the compounds published in the last five years, which showed promising activity in GBM preclinical models acting as TKIs. We grouped the compounds based on the targeted kinase: first, we reported receptor TKIs and then, cytoplasmic and peculiar kinase inhibitors. For each small molecule, we included the chemical structure, and we schematized the interaction with the target for some representative compounds with the aim of elucidating the mechanism of action. Finally, we cited the most relevant clinical trials.

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Tivantinib Hampers the Proliferation of Glioblastoma Cells via PI3K/Akt/Mammalian Target of Rapamycin (mTOR) Signaling

Cited by 5 publications

References 42 publications

Drug Repurposing in Dentistry: Towards Application of Small Molecules in Dentin Repair

Drug Repurposing in Dentistry: Towards Application of Small Molecules in Dentin Repair

Ropivacaine represses the ovarian cancer cell stemness and facilitates cell ferroptosis through inactivating the PI3K/AKT signaling pathway

Small Molecule Tyrosine Kinase Inhibitors (TKIs) for Glioblastoma Treatment

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