Vinorelbine for non-small cell lung cancer

Piccirillo, Maria Carmela; Daniele, Gennaro; Maïo, Massimo Di; Bryce, Jane; Feo, Gianfranco De; Giudice, Antonia Del; Perrone, Francesco; Morabito, Alessandro

doi:10.1517/14740331003774078

Cited by 16 publications

(12 citation statements)

References 83 publications

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“…A variety of mechanisms have been implicated in resistance, including reduced accumulation of the drug, increased levels of glutathione (GSH), enhanced expression of metallothionein (MT), enhanced DNA repair, overexpression of antiapoptotic Bcl-2, and alterations in signal transduction pathways involved in apoptosis (1)(2)(3)(4)(5). As part of the extensive research into the mechanism of action of cisplatin, combinations with other chemotherapeutics have been developed to treat a variety of solid tumors that are unresponsive to cisplatin itself (6)(7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Capsaicin Induces Apoptosis of Cisplatin-Resistant Stomach Cancer Cells by Causing Degradation of Cisplatin-Inducible Aurora-A Protein

Huh

Lee

et al. 2011

Nutrition and Cancer

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Various chemotherapeutic agents such as cisplatin have been used to treat gastric cancer. However, a substantial number of patients acquire resistance to this treatment, and this is followed by rapid relapse of the disease. We investigated the anticancer effect of capsaicin, the active ingredient in red pepper, in the cisplatin-resistant Korean human gastric cancer cell line SNU-668. We found that treatment of SNU-668 cells with capsaicin in combination with cisplatin induced higher apoptotic cell death than that of treatment with either capsaicin or cisplatin alone. Furthermore, we discovered that Aurora-A protein increased in response to cisplatin and was degraded upon combined treatment with capsaicin with cisplatin, suggesting that the Aurora-A-mediated signaling pathway is responsible for the resistance to cisplatin in cisplatin-resistant gastric cancer cell lines. Combined treatment with capsaicin and cisplatin induced G1/S arrest, whereas cisplatin alone caused accumulation in G2/M. Combined treatment with capsaicin and cisplatin inhibited IκB phosphorylation in a dose-dependent manner, suggesting that Aurora-A directly or indirectly regulates NF-κB translocation. We propose that combined administration of cisplatin and capsaicin may provide a strategy for overcoming cisplatin resistance.

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Section: Introductionmentioning

confidence: 99%

Capsaicin Induces Apoptosis of Cisplatin-Resistant Stomach Cancer Cells by Causing Degradation of Cisplatin-Inducible Aurora-A Protein

Huh

Lee

et al. 2011

Nutrition and Cancer

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“…Drugs that influence microtubule dynamics have been a core in cancer treatment for decades. Vinorelbine, a third-generation vinca alkaloid approved for NSCLC treatment by inhibiting microtubule dynamics, either monotherapy or combination with other cancer medications enhances the survival of patients with advanced NSCLC [ 1 , 2 ]. However, treatment toxicities may occur, such as neutropenia, leucopenia, edema, bruising, bleeding, anemia, hair loss, and peripheral neuropathy [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Neutropenia is the most common toxicity to discontinue the administration of the medication. Reducing the dose intensity through combination therapy or changing administration schedule is the strategy to improve the tolerability of vinorelbine [ 1 , 4 ]. However, the development of novel drug combination is still needed in improving drug efficacy and increasing tolerability.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel Agents on Spindle Assembly Checkpoint to Sensitize Vinorelbine-Induced Mitotic Cell Death against Human Non-Small Cell Lung Cancers

Chang

Tseng

Leu

et al. 2020

IJMS

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Non-small cell lung cancer (NSCLC) accounts about 80% of all lung cancers. More than two-thirds of NSCLC patients have inoperable, locally advanced or metastatic tumors. Non-toxic agents that synergistically potentiate cancer-killing activities of chemotherapeutic drugs are in high demand. YL-9 was a novel and non-cytotoxic compound with the structure related to sildenafil but showing much less activity against phosphodiesterase type 5 (PDE5). NCI-H460, an NSCLC cell line with low PDE5 expression, was used as the cell model. YL-9 synergistically potentiated vinorelbine-induced anti-proliferative and apoptotic effects in NCI-H460 cells. Vinorelbine induced tubulin acetylation and Bub1-related kinase (BUBR1) phosphorylation, a necessary component in spindle assembly checkpoint. These effects, as well as BUBR1 cleavage, were substantially enhanced in co-treatment with YL-9. Several mitotic arrest signals were enhanced under combinatory treatment of vinorelbine and YL-9, including an increase of mitotic spindle abnormalities, increased cyclin B1 expression, B-cell lymphoma 2 (Bcl-2) phosphorylation and increased phosphoproteins. Moreover, YL-9 also displayed synergistic activity in combining with vinorelbine to induce apoptosis in A549 cells which express PDE5. In conclusion. the data suggest that YL-9 is a novel agent that synergistically amplifies vinorelbine-induced NSCLC apoptosis through activation of spindle assembly checkpoint and increased mitotic arrest of the cell cycle. YL-9 shows the potential for further development in combinatory treatment against NSCLC.

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“…Vinorelbine is a cytotoxic vinca alkaloid with welldocumented effects in non-small cell lung cancer (NSCLC) [1] and advanced breast cancer [2]. It was the first of the socalled third-generation cytotoxic drugs which was shown to be more effective in NSCLC than its predecessors among "second-generation" cytotoxic drugs, e.g.…”

Section: Introductionmentioning

confidence: 99%

“…As with most other cytotoxic drugs, the dose-limiting toxicity of vinorelbine is haematologic, with neutropenia as the most common side effect [1]. Among non-haematologic side effects, neurotoxicity, nausea and constipation are commonly seen.…”

Section: Introductionmentioning

confidence: 99%

Prophylactic treatment of local reactions to i.v. vinorelbine: a randomized study

Quant

Bergman

2011

Support Care Cancer

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Vinorelbine for non-small cell lung cancer

Abstract: Vinorelbine is an active and generally manageable therapeutic option for the treatment of both early and advanced NSCLC.

Cited by 16 publications

References 83 publications

Capsaicin Induces Apoptosis of Cisplatin-Resistant Stomach Cancer Cells by Causing Degradation of Cisplatin-Inducible Aurora-A Protein

Capsaicin Induces Apoptosis of Cisplatin-Resistant Stomach Cancer Cells by Causing Degradation of Cisplatin-Inducible Aurora-A Protein

Discovery of Novel Agents on Spindle Assembly Checkpoint to Sensitize Vinorelbine-Induced Mitotic Cell Death against Human Non-Small Cell Lung Cancers

Prophylactic treatment of local reactions to i.v. vinorelbine: a randomized study

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