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
Inhibition of protein nitration prevents cisplatin-induced inactivation of STAT3 and promotes anti-apoptotic signaling in organ of Corti cells.
TL;DR: Results suggest that the inhibition of cisplatin-induced nitration prevents the inactivation of STAT3, which in turn enables the transcription of anti-apoptotic genes and thereby helps to mitigate cisplarin-induced toxicity.
Journal ArticleDOI
Zingerone protects against cisplatin-induced oxidative damage in the jejunum of Wistar rats
Muneeb U. Rehman,Bilal Ahmad,Ahmad Arif,Saiema Rasool,Adil Farooq,Rahil Razzaq,Showkat Ahmad Bhat,Sumaira Bashir,Ovais Shabir,Insha Amin,Mubashir Hussain Masoodi,Manzoor Ur Rahman Mir,Mohammed Yaseen Shah +12 more
TL;DR: These experiments strongly indicate that zingerone treatment exercises a protective efficacy by suppressing both oxidative stress and inflammation through the modulation of key pro-inflammatory cytokine and transcription factors.
Journal ArticleDOI
Cisplatin resistance in lung cancer is mediated by MACC1 expression through PI3K/AKT signaling pathway activation.
TL;DR: The results revealed that MACC1 increased Cis-Re partially via the PI3K/AKT signaling pathway, suggesting thatMACC1 could serve as a potential target to overcome C is-Re.
Journal ArticleDOI
In vivo hepatoprotective effect of Morinda elliptica stem extract against liver fibrosis induced by thioacetamide.
Sarwan W. Bradosty,Sarwan W. Bradosty,Saber W. Hamad,Nabaz Fisal Shakir Agha,Faiyaz K. Shaikh,Nadir Mustafa Qadir Nanakali,Nadir Mustafa Qadir Nanakali,Peshawa Yunis Aziz,Nur'Ain Salehen,Faruk Süzergöz,Mahmood Ameen Abdulla +10 more
TL;DR: In this paper, the in vivo hepatoprotective activity of ethanolic extract of M. elliptica stem in thioacetamide (TAA) induced liver fibrosis in male Sprague Drawly rats.
Journal ArticleDOI
Correction: Aqueous extract of Cordyceps sinensis potentiates the antitumor effect of DDP and attenuates therapy-associated toxicity in non-small cell lung cancer via IκBα/NFκB and AKT/MMP2/MMP9 pathways
Xiaowei Huo,Xiaowei Huo,Chenqi Liu,Chenqi Liu,Xue-Lian Bai,Xue-Lian Bai,Wenjia Li,Jing Li,Xue-Feng Hu,Li Cao +9 more
TL;DR: Aqueous extract of Cordyceps sinensis potentiates the antitumor effect of DDP and attenuates therapy-associated toxicity in non-small cell lung cancer via IκBα/NFκB and AKT/MMP2/M MP9 pathways.
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.
Book
Molecular Aspects of Anticancer Drug-DNA Interactions
Stephen Neidle,Michael J. Waring +1 more
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.