Nedaplatin sensitization of cisplatin-resistant human non-small cell lung cancer cells

Wang, Huan; Zhu, Xiaoli; Huang, Jing; Chen, Pingsheng; Han, Shuhua; Xing, Yan

doi:10.3892/ol.2016.4276

Cited by 7 publications

(6 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inhibition of these cyclins and CDKs results in the accumulation of cells in the S-phase (41). Other researchers have shown that cisplatin can arrest the cell cycle of A549 cells in the S-phase (30,42) or in G 2 /M phase (34). Cell-cycle arrest is a possible mechanism for growth inhibition and induction of apoptosis in A549 cells by platinum complexes.…”

Section: Discussionmentioning

confidence: 94%

“…The ability of cisplatin to induce apoptotic cell death has already been reported not only for lung cancer cells (30) but also in other tumour cell lines of prostate (31), gastric (32) and bladder (33) cancer. Moreover, other newly synthesized platinum-based drugs induced apoptosis of different cell lines (14,(34)(35). Cisplatin and other platinum-based drugs induce apoptosis through several different mechanisms including activation of pro-apoptotic genes such as p53 upregulated modulator of apoptosis (PUMA) (36), caspases (37), P53-induced protein with a death domain (PIDD) (38), mitogen-activated protein kinase (MAPK) family (39), as well as through interaction with BCL2 family proteins in mitochondria or the cytosol (40).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Effects of Newly Synthesized Platinum(IV) Complexes on Cytotoxicity and Radiosensitization of Human Tumour Cells In Vitro

et al. 2020

View full text Add to dashboard Cite

Aim: Newly synthesized platinum(IV) complexes with ethylenediamine-N,N'-diacetate ligands (EDDA-type) (butyl-Pt and pentyl-Pt) were investigated against two cancer (A549 lung, and HTB 140 melanoma) and one noncancerous (MRC-5 embryonic lung fibroblast) human cell lines. Materials and Methods: The effects of these agents were compared with those of cisplatin after 6-, 24-and 48-h treatment. Sulforhodamine-B (SRB) assay was performed to estimate the cytotoxic effect, while the inhibitory effect on cell proliferation was measured using 5-bromo-2,deoxyuridine (BrdU) incorporation assay. Cell cycle analysis was performed by flow cytometry. Type of cell death induced by these agents was determined by electrophoretic analysis of DNA, flow cytometry and by western blot analysis of proteins involved in induction of apoptosis. The effects of gamma irradiation, alone and in combination with platinumbased compounds, were examined by clonogenic and SRB assays. Results: All examined platinum-based compounds had inhibitory and antiproliferative effects on A549 cells, but not on HTB140 and MRC-5 cells. Butyl-Pt, pentyl-Pt and cisplatin arrested the cell cycle in the S-phase and induced apoptotic cell death via regulation of expression of B-cell lymphoma 2 (BCL2) and BCL2-associated X (BAX) proteins. Platinum-based compounds increased the sensitivity of A549 cells to gamma irradiation. Butyl-Pt and pentyl-Pt showed better antitumour effects against A549 cells than did cisplatin, by interfering in cell proliferation and the cell cycle, and by triggering apoptosis. Conclusion: The effects of gamma irradiation on tumour cells may be amplified by pre-treatment of cells with platinum-based compounds.Cisplatin or cis-diamminedichloroplatinum(II) is an effective chemotherapeutic agent that is used in nearly 50% of all patients with cancer (1). It has been used in the fight against ovarian, head and neck, bladder, cervical, oesophageal, as well as against small-cell and non-small-cell lung cancer. The clinical utility of cisplatin is based on the inhibition of the processes that are important for growth and proliferation of cancer cells by binding to DNA molecules and preventing replication, transcription and cell-cycle progression, leading to tumour cell death (2, 3). However, cisplatin administration is associated with adverse effects and therapy resistance. The development of platinum analogues that have similar effectiveness as cisplatin but better toxicity profiles and lack cross-resistance is the major concern in research centres worldwide. Different modifications of cisplatin have been investigated to achieve this aim.Platinum complexes are widely used in cancer therapy research. Approximately 30 platinum(II) and platinum(IV) 5001

show abstract

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

The Effects of Newly Synthesized Platinum(IV) Complexes on Cytotoxicity and Radiosensitization of Human Tumour Cells In Vitro

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A549 is a non-small cell lung cancer (NSCLC) cell line, the main cancer type nedaplatin is used for treating. A large number of publications have studied the antiproliferative effect of nedaplatin in NSCLC, with a few studies investigating the expression of apoptotic markers and altered cell cycle distribution in response to nedaplatin treatment [ 20 , 26 , 27 , 28 ]. However, genotoxicity or DNA damage induction, assumed to be the main mechanism of action of all platinum drugs, are not assessed in any of these publications and will be addressed in this study.…”

Section: Resultsmentioning

confidence: 99%

Encapsulation of Nedaplatin in Novel PEGylated Liposomes Increases Its Cytotoxicity and Genotoxicity against A549 and U2OS Human Cancer Cells

et al. 2020

View full text Add to dashboard Cite

Following the discovery of cisplatin over 50 years ago, platinum-based drugs have been a widely used and effective form of cancer therapy, primarily causing cell death by inducing DNA damage and triggering apoptosis. However, the dose-limiting toxicity of these drugs has led to the development of second and third generation platinum-based drugs that maintain the cytotoxicity of cisplatin but have a more acceptable side-effect profile. In addition to the creation of new analogs, tumor delivery systems such as liposome encapsulated platinum drugs have been developed and are currently in clinical trials. In this study, we have created the first PEGylated liposomal form of nedaplatin using thin film hydration. Nedaplatin, the main focus of this study, has been exclusively used in Japan for the treatment of non-small cell lung cancer, head and neck, esophageal, bladder, ovarian and cervical cancer. Here, we investigate the cytotoxic and genotoxic effects of free and liposomal nedaplatin on the human non-small cell lung cancer cell line A549 and human osteosarcoma cell line U2OS. We use a variety of assays including ICP MS and the highly sensitive histone H2AX assay to assess drug internalization and to quantify DNA damage induction. Strikingly, we show that by encapsulating nedaplatin in PEGylated liposomes, the platinum uptake cytotoxicity and genotoxicity of nedaplatin was significantly enhanced in both cancer cell lines. Moreover, the enhanced platinum uptake as well as the cytotoxic/antiproliferative effect of liposomal nedaplatin appears to be selective to cancer cells as it was not observed on two noncancer cell lines. This is the first study to develop PEGylated liposomal nedaplatin and to demonstrate the superior cell delivery potential of this product.

show abstract

“…It was approved in Japan for use in several cancers, including SCLC [46]. It has been allowed to be used in the treatment of esophageal cancer, lung cancer, gynecological cancer, head and neck tumors in China based on the results of many clinical trials, which showed that nedaplatin has similar anti-tumor therapeutic effects with a lower toxicity than cisplatin [47][48][49][50]. The common adverse effects of nedaplatin include bone marrow suppression, gastrointestinal symptoms, kidney dysfunction, ototoxicity, and alopecia, while allergic reaction and Adams-Stokes syndrome are rare complications [51].…”

Section: Discussionmentioning

confidence: 99%

Severe rhabdomyolysis associated with etoposide-nedaplatin chemotherapy in a patient with small cell lung cancer：case report and review of literature

Xu¹,

Xiao²,

Zhang³

et al. 2022

Preprint

View full text Add to dashboard Cite

Etoposide combined with platinum drugs is the first-line chemotherapy for small cell lung cancer（SCLC）. Here, we describe the first case with small cell lung cancer, who developed severe rhabdomyolysis after etoposide-nedaplatin chemotherapy. He complained of progressive generalized muscle pain and weakness after first cycle chemotherapy for SCLC, accompanied by elevated creatine kinase (CK), myoglobin (Mb), alanine aminotransferase (ALT), spartate aminotransferase (AST) and lactate dehydrogenase (LDH). Examination and inquiry of medical history were used to exclude the factors of rhabdomyolysis caused by trauma, strenuous activities, infections, hyperthermia and immunity, the patient was diagnosed with severe rhabdomyolysis induced by chemotherapy. After treatment with intravenous fluids and methylprednisolone, the patient’s symptoms were relieved and laboratory tests were significantly improved. An unexpected situation is that the lung CT scan showed that the lung mass was significantly smaller than that before chemotherapy, but the reason is not clear. Rhabdomyolysis induced by anti-cancer drugs, especially chemotherapy drugs, is rarely reported and easily overlooked. Therefore, physicians should be aware of this rare but potentially serious complication when using chemotherapy drugs.

show abstract

Nedaplatin sensitization of cisplatin-resistant human non-small cell lung cancer cells

Cited by 7 publications

References 30 publications

The Effects of Newly Synthesized Platinum(IV) Complexes on Cytotoxicity and Radiosensitization of Human Tumour Cells In Vitro

The Effects of Newly Synthesized Platinum(IV) Complexes on Cytotoxicity and Radiosensitization of Human Tumour Cells In Vitro

Encapsulation of Nedaplatin in Novel PEGylated Liposomes Increases Its Cytotoxicity and Genotoxicity against A549 and U2OS Human Cancer Cells

Severe rhabdomyolysis associated with etoposide-nedaplatin chemotherapy in a patient with small cell lung cancer：case report and review of literature

Contact Info

Product

Resources

About