Mitochondrial Involvement in Cisplatin Resistance
Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a cha...
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| Veröffentlicht in: | International journal of molecular sciences 2019-07, Vol.20 (14), p.3384 |
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| description | Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary. |
| doi_str_mv | 10.3390/ijms20143384 |
| format | Article |
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Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20143384</identifier><identifier>PMID: 31295873</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Adenosine triphosphate ; Amino acids ; Animals ; Antineoplastic Agents - pharmacology ; Antioxidants ; Apoptosis ; Bioenergetics ; Biosynthesis ; Calcium ; Calcium ions ; Cancer therapies ; Cell death ; Cell Nucleus - metabolism ; Cellular structure ; Chemotherapy ; Cisplatin ; Cisplatin - pharmacology ; Cytotoxicity ; Damage tolerance ; Deoxyribonucleic acid ; Detoxification ; DNA ; DNA repair ; DNA, Mitochondrial ; Drug development ; Drug Resistance, Neoplasm ; Drugs ; Efflux ; Formulations ; Homeostasis ; Humans ; Lipid metabolism ; Lipids ; Metabolism ; Mitochondria ; Mitochondria - drug effects ; Mitochondria - genetics ; Mitochondria - metabolism ; Mitochondrial DNA ; Mitochondrial Dynamics - drug effects ; Mitophagy - drug effects ; Neoplasms - drug therapy ; Neoplasms - metabolism ; Nucleic acids ; Nucleotides ; Ovarian cancer ; Oxidation ; Oxidative phosphorylation ; Phosphorylation ; Platinum ; Platinum compounds ; Proteins ; Review ; Rewiring ; Signal Transduction ; Tricarboxylic acid cycle ; Tumors</subject><ispartof>International journal of molecular sciences, 2019-07, Vol.20 (14), p.3384</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). 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Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.</description><subject>Adenosine triphosphate</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Bioenergetics</subject><subject>Biosynthesis</subject><subject>Calcium</subject><subject>Calcium ions</subject><subject>Cancer therapies</subject><subject>Cell death</subject><subject>Cell Nucleus - metabolism</subject><subject>Cellular structure</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Cytotoxicity</subject><subject>Damage tolerance</subject><subject>Deoxyribonucleic acid</subject><subject>Detoxification</subject><subject>DNA</subject><subject>DNA repair</subject><subject>DNA, Mitochondrial</subject><subject>Drug development</subject><subject>Drug Resistance, Neoplasm</subject><subject>Drugs</subject><subject>Efflux</subject><subject>Formulations</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Lipid metabolism</subject><subject>Lipids</subject><subject>Metabolism</subject><subject>Mitochondria</subject><subject>Mitochondria - 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pharmacology</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Bioenergetics</topic><topic>Biosynthesis</topic><topic>Calcium</topic><topic>Calcium ions</topic><topic>Cancer therapies</topic><topic>Cell death</topic><topic>Cell Nucleus - metabolism</topic><topic>Cellular structure</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Cytotoxicity</topic><topic>Damage tolerance</topic><topic>Deoxyribonucleic acid</topic><topic>Detoxification</topic><topic>DNA</topic><topic>DNA repair</topic><topic>DNA, Mitochondrial</topic><topic>Drug development</topic><topic>Drug Resistance, Neoplasm</topic><topic>Drugs</topic><topic>Efflux</topic><topic>Formulations</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Lipid metabolism</topic><topic>Lipids</topic><topic>Metabolism</topic><topic>Mitochondria</topic><topic>Mitochondria - drug effects</topic><topic>Mitochondria - genetics</topic><topic>Mitochondria - metabolism</topic><topic>Mitochondrial DNA</topic><topic>Mitochondrial Dynamics - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cocetta, Veronica</au><au>Ragazzi, Eugenio</au><au>Montopoli, Monica</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mitochondrial Involvement in Cisplatin Resistance</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-07-10</date><risdate>2019</risdate><volume>20</volume><issue>14</issue><spage>3384</spage><pages>3384-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31295873</pmid><doi>10.3390/ijms20143384</doi><orcidid>https://orcid.org/0000-0001-6182-4132</orcidid><orcidid>https://orcid.org/0000-0002-0390-6823</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adenosine triphosphate Amino acids Animals Antineoplastic Agents - pharmacology Antioxidants Apoptosis Bioenergetics Biosynthesis Calcium Calcium ions Cancer therapies Cell death Cell Nucleus - metabolism Cellular structure Chemotherapy Cisplatin Cisplatin - pharmacology Cytotoxicity Damage tolerance Deoxyribonucleic acid Detoxification DNA DNA repair DNA, Mitochondrial Drug development Drug Resistance, Neoplasm Drugs Efflux Formulations Homeostasis Humans Lipid metabolism Lipids Metabolism Mitochondria Mitochondria - drug effects Mitochondria - genetics Mitochondria - metabolism Mitochondrial DNA Mitochondrial Dynamics - drug effects Mitophagy - drug effects Neoplasms - drug therapy Neoplasms - metabolism Nucleic acids Nucleotides Ovarian cancer Oxidation Oxidative phosphorylation Phosphorylation Platinum Platinum compounds Proteins Review Rewiring Signal Transduction Tricarboxylic acid cycle Tumors |
| title | Mitochondrial Involvement in Cisplatin Resistance |
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