Journal ArticleDOI
Molecular basis of cellular response to cisplatin chemotherapy in non-small cell lung cancer (Review)
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TLDR
In this review, insights are provided into the pathways involved in cisplatin damage from entering the cells to execution of apoptosis or survival of NSCLC cells and this knowledge should provide a basis for further studies to improve the understanding of molecular events associated with lung cancer.Abstract:
Cisplatin is one of the most potent anticancer agents, displaying significant clinical activity against a variety of solid tumors. For more than two decades, the most effective systemic chemotherapy for non-small cell lung cancer (NSCLC), the leading cause of cancer morbidity and mortality among men and women in the western world, was cisplatin-based combination treatment. Unfortunately, the outcome of cisplatin therapy on NSCLC seems to have reached a plateau. Therefore, the biological mechanisms of cisplatin action need to be understood in order to overcome the treatment plateau on NSCLC. Moreover, the development of resistance is a hurdle in the use of this drug. The molecular mechanisms that underlie this chemoresistance are largely unknown. Possible mechanisms of acquired resistance to cisplatin include reduced intracellular accumulation of cisplatin, enhanced drug inactivation by metallothionine and glutathione, increased repair activity of DNA damage, and altered expression of oncogenes and regulatory proteins. In addition, it is generally accepted that cytotoxicity of cisplatin is mediated through induction of apoptosis and arrest of cell cycle resulting from its interaction with DNA, such as the formation of cisplatin-DNA adducts, which activates multiple signaling pathways, including those involving p53, Bcl-2 family, caspases, cyclins, CDKs, pRb, PKC, MAPK and PI3K/Akt. Increased expression of anti-apoptotic genes and mutations in the intrinsic apoptotic pathway may contribute to the inability of cells to detect DNA damage or to induce apoptosis. Towards an understanding of the molecular basis of the cellular response to cisplatin-based chemotherapy in NSCLC, in this review we provide some insights into the pathways involved in cisplatin damage from entering the cells to execution of apoptosis or survival of NSCLC cells. We believe that as more and more molecular mechanisms of response to cisplatin-based therapy are unraveled, this knowledge should provide a basis for further studies to improve our understanding of molecular events associated with lung NSCLC as well as to devise novel and effective therapeutic approaches to overcome the treatment plateau or reverse drug resistance in this disease.read more
Citations
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Journal ArticleDOI
Differences in the cellular response and signaling pathways between cisplatin and monodentate organometallic Ru(II) antitumor complexes containing a terphenyl ligand
Anna Kisova,Lenka Zerzankova,Abraha Habtemariam,Peter J. Sadler,Viktor Brabec,Jana Kasparkova +5 more
TL;DR: Complex 1 may provide an alternative therapy in patients with acquired cisplatin resistance, particularly with respect to its very low mutagenicity and different mode of action compared to platinum antitumor drugs in clinical use.
Journal ArticleDOI
Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity
Masashi Shiiba,Hitomi Yamagami,Ayumi Yamamoto,Yasuyuki Minakawa,Atsushi Okamoto,Atsushi Kasamatsu,Yosuke Sakamoto,Katsuhiro Uzawa,Yuichi Takiguchi,Hideki Tanzawa +9 more
TL;DR: The present study suggests that AKR1C family is closely associated with drug resistance to CDDP and 5-FU, and mefenamic acid enhances their sensitivity through its inhibitory activity in drug-resistant human cancer cells.
Journal ArticleDOI
Sphingolipids and the sphingosine kinase inhibitor, SKI II, induce BCL-2-independent apoptosis in human prostatic adenocarcinoma cells.
M.E. Leroux,Edmond Auzenne,Randall L. Evans,N. Hail,W. Spohn,Sukhen C. Ghosh,David Farquhar,T. McDonnell,Jim Klostergaard +8 more
TL;DR: Elevated BCL‐2 is one mechanism of therapeutic resistance in prostate cancer (PC), and new approaches are needed to overcome such resistance.
Journal ArticleDOI
miR-539 enhances chemosensitivity to cisplatin in non-small cell lung cancer by targeting DCLK1.
TL;DR: In this paper, the authors found that miR-539 was significantly downregulated in DDP-resistant cell lines (A549/DDP and H1299-DDP) and showed that downregulation of miR539 inhibited the sensitivity of parental NSCLC cells to DDP by promoting cell proliferation and decreasing DDPinduced apoptosis.
Journal ArticleDOI
Mitochondrial fusion: a mechanism of cisplatin-induced resistance in neuroblastoma cells?
Giada Santin,Valeria Maria Piccolini,Sergio Barni,Paola Veneroni,Vincenzo Giansanti,Veronica Dal Bo,Graziella Bernocchi,Maria Grazia Bottone +7 more
TL;DR: In recovered and re-seeded cells, mitochondrial equilibrium moved toward fusion, possibly protecting cells from apoptosis, and cisplatin-induced mitochondrial functional and morphological long-term effects in neuroblastoma B50 rat cells were investigated.
References
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BookDOI
Cisplatin : chemistry and biochemistry of a leading anticancer drug
TL;DR: The start: platinum complexes for the treatment of cancer - why the search goes on and new developments: structure-activity relationships within di- and trinuclear platinum phase I clinical anticancer agents the development of orally-active platinum drugs methods for screening the potential antitumor activity of platinum compounds in combinatorial libraries computational studies on platinum antitumors complexes and their adducts with nucleid acids constituents.
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Molecular Aspects of Anticancer Drug-DNA Interactions
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TL;DR: The cellular and molecular pharmacology of the anthrapyrazole antitumour agent and the mitomycins - natural cross-linkers of DNA, M.D. Wilson and F.A. Tomasz are studied.
Journal ArticleDOI
Piecing Together the p53 Puzzle
TL;DR: New findings showing that the checkpoint kinase CHK2 regulates a crucial central player in checkpoint pathways-the tumor suppressor protein p53 are discussed.