Cervical Cancer Cell Growth, Drug Resistance, and Epithelial-Mesenchymal Transition Are Suppressed by g-Secretase Inhibitor RO4929097

Wang, Lu; Dai, Guo; Yang, Jian; Wu, Wanrong; Zhang, Wei

doi:10.12659/msm.909452

Cited by 17 publications

(12 citation statements)

References 37 publications

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“…Furthermore, the molecular therapeutics targeting key biomarkers such as EGFR receptors showed some success in clinical trials, but the cancer stem cell-derived drug resistance hindered the drug effects [152] . Recently, Shang et al [71] found that Notch signaling is expressed in both CD133+ and CD133-cells. However, the activation of Notch signaling in CD133+ cells leads to a higher proliferation rate and lower apoptosis and results in targeted-therapy resistance, compared to CD133-cells.…”

Section: Notch Signaling and Cscsmentioning

confidence: 99%

“…Findings from xenograft experiments further demonstrated that CD133+ cells are able to retain a higher tumorigenic capacity than their counterpart, thus indicating their tumor-initiating feature. In addition, Notch inhibition by DAPT combined with EGFR inhibitor (AG1478) treatment on EC cells displays ameliorative effects compared to DAPT or AG1478 treatments alone, thus reducing the CD133+ cells viability [71] .…”

Section: Notch Signaling and Cscsmentioning

confidence: 99%

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Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Giuli¹,

Mancusi²,

Giuliani³

et al. 2021

CDR

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Drug resistance is one of the main challenges in cancer therapy, including in the treatment of female-specific malignancies, which account for more than 60% of cancer cases among women. Therefore, elucidating the underlying molecular mechanisms is an urgent need in gynecological cancers to foster novel therapeutic approaches. Notably, Notch signaling, including either receptors or ligands, has emerged as a promising candidate given its multifaceted role in almost all of the hallmarks of cancer. Concerning the connection between Notch pathway and drug resistance in the afore-mentioned tumor contexts, several studies focused on the Notchdependent regulation of the cancer stem cell (CSC) subpopulation or the induction of the epithelial-tomesenchymal transition (EMT), both features implicated in either intrinsic or acquired resistance. Indeed, the present review provides an up-to-date overview of the published results on Notch signaling and EMT-or CSCdriven drug resistance. Moreover, other drug resistance-related mechanisms are examined such as the involvement of the Notch pathway in drug efflux and tumor microenvironment. Collectively, there is a long way to go before every facet will be fully understood; nevertheless, some small pieces are falling neatly into place. Overall, the main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.

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Section: Notch Signaling and Cscsmentioning

confidence: 99%

Section: Notch Signaling and Cscsmentioning

confidence: 99%

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Giuli¹,

Mancusi²,

Giuliani³

et al. 2021

CDR

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“…RO4929097reduces the chemoresistance and metastasis in CC cells [31]. SiHa) compared with HPV-negative cell line (C-33A).…”

Section: Notch Signaling Pathwaymentioning

confidence: 99%

Signaling Pathways in Cervical Cancer Chemoresistance: Are microRNAs and Long-Noncoding RNAs the Main Culprits?

Mousavi¹,

Hemmat²,

Baghi³

et al. 2020

Preprint

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Cervical cancer is known as one of the most important cancers in women worldwide. Chemotherapy is a standard treatment for advanced/recurrent cervical cancer in which the prognosis of the disease is really poor and the 1-year survival chance in these patients is maximally 20%. However, resistance to anticancer drugs is a major problem in treating cancer. Cervical cancer stem cells are considered as a fundamental cause of chemo and radio-resistance and also relapse after primary successful treatment. Signaling pathways include a wide range of molecular mechanisms contribute to drug resistance. Recently, microRNAs (miRNAs) are announced as a group of molecular biomarkers involving in response to chemotherapy in cancer patients. As the miRNAs, there are some long non-coding RNAs (LncRNAs) which their aberrant expression is considered as a biomarker for monitoring chemoresistance. In this review, we summarized current reports about the involvement of signaling pathways during chemoresistance in cervical cancer. Then, genes that have been demonstrated their involvement during drug resistance in cervical cancer were tabulated. Further, miRNAs that have been reported as biomarkers during treatment are listed. By bioinformatic analysis, we predictedmiR-335-5p and miR-16-5p as the most potential biomarkers for monitoring resistance to chemotherapy. Finally, long non-coding RNAs that have been introduced in recent studies as novel biomarkers during the response to chemotherapy were mentioned.

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“…Despite initial therapeutic response, the majority of patients either undergo relapse or succumb to the disease as a result of resistance to chemotherapy [ 15 ]. Chemoresistance is the most important factor that decreases or abrogates the efficacy of chemotherapy in many cancers including advanced cervical cancer, producing an increase in tumor progression, which results in high rates of cancer-related deaths [ 16 , 17 ]. Many factors contribute to chemoresistance, including but not limited to, alterations in DNA damage and repair capacity, and overexpression of ATP-binding cassette (ABC) transporters, notably the ABCB1 transporter [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe

et al. 2021

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In this study, we designed, synthesized and evaluated, in vitro, novel chalcone analogs containing dialkylamino pharmacophores in the cervical cancer cell line, OV2008. The compound, DML6 was selective and significantly decreased the proliferation of OV2008 and HeLa cells in sub-micromolar concentrations, compared to prostate, lung, colon, breast or human embryonic kidney cell line (HEK293). DML6, at 5 μM, arrested the OV2008 cells in the G2 phase. Furthermore, DML6, at 5 μM, increased the levels of reactive oxygen species and induced a collapse in the mitochondrial membrane potential, compared to OV2008 cells incubated with a vehicle. DML6, at 5 μM, induced intrinsic apoptosis by significantly (1) increasing the levels of the pro-apoptotic proteins, Bak and Bax, and (2) decreasing the levels of l the anti-apoptotic protein, Bcl-2, compared to cell incubated with a vehicle. Furthermore, DML6, at 5 and 20 μM, induced the cleavage of caspase-9, followed by subsequent cleavage of the executioner caspases, caspase-3 and caspase-7, which produced OV2008 cell death. Overall, our data suggest that DML6 is an apoptosis-inducing compound that should undergo further evaluation as a potential treatment for cervical cancer.

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Cervical Cancer Cell Growth, Drug Resistance, and Epithelial-Mesenchymal Transition Are Suppressed by g-Secretase Inhibitor RO4929097

Cited by 17 publications

References 37 publications

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Notch signaling in female cancers: a multifaceted node to overcome drug resistance

Signaling Pathways in Cervical Cancer Chemoresistance: Are microRNAs and Long-Noncoding RNAs the Main Culprits?

A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe

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