Kinase inhibitor screening reveals aurora‐a kinase is a potential therapeutic and prognostic biomarker of gastric cancer
Gastric cancer is one of the most common and deadly types of cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric cancer. Here, we explore the antiprolifera...
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| Veröffentlicht in: | Journal of cellular biochemistry 2021-10, Vol.122 (10), p.1376-1388 |
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| creator | Mesquita, Felipe P. Lucena da Silva, Emerson Souza, Pedro F. N. Lima, Luina B. Amaral, Jackson L. Zuercher, William Albuquerque, Louise M. Rabenhorst, Silvia H. B. Moreira‐Nunes, Caroline A. Amaral de Moraes, Maria E. Montenegro, Raquel C. |
| description | Gastric cancer is one of the most common and deadly types of cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric cancer. Here, we explore the antiproliferative and antimigratory effects of the AURKA inhibitor and the prognostic and therapeutic value as a biomarker of gastric cancer. A total of 145 kinase inhibitors were screened to evaluate the cytotoxic or cytostatic effects in the gastric cancer cell line. Using the Alamar Blue assay, flow cytometry, quantitative polymerase chain reaction, and observation of caspase 3/7 activity and cell migration, we investigated the antiproliferative, proapoptotic, and antimigratory effects of the AURKA inhibitor. Moreover, AURKA overexpression was evaluated in the gastric cell lines and the gastric tumor tissue. Out of the 145 inhibitors, two presented the highest antiproliferative effect. Both molecules can induce apoptosis by the caspases 3/7 pathway in addition to inhibiting cancer cell migration, mainly the AURKA inhibitor. Moreover, molecular docking analysis revealed that GW779439X interacts in the active site of the AURKA enzyme with similar energy as a well‐described inhibitor. Our study identified AURKA overexpression in the gastric cancer cell line and gastric tumor tissue, revealing that its overexpression in patients with cancer is correlated with low survival. Therefore, it is feasible to suggest AURKA as a potential marker of gastric cancer, besides providing robust information for diagnosis and estimated survival of patients. AURKA can be considered a new molecular target used in the prognosis and therapy of gastric cancer.
Our study demonstrated the antitumoral effects of Aurora‐A kinase inhibitor against gastric cancer cell line, as well as the overexpression of AURKA gene and its relationship with poor survival of gastric cancer patients |
| doi_str_mv | 10.1002/jcb.30015 |
| format | Article |
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Our study demonstrated the antitumoral effects of Aurora‐A kinase inhibitor against gastric cancer cell line, as well as the overexpression of AURKA gene and its relationship with poor survival of gastric cancer patients</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.30015</identifier><identifier>PMID: 34160883</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - pharmacology ; Antiproliferatives ; Apoptosis ; AURKA ; Aurora Kinase A - antagonists & inhibitors ; Aurora Kinase A - metabolism ; biomarker ; Biomarkers ; Cancer ; Caspase-3 ; Cell adhesion & migration ; Cell Line, Tumor ; Cell migration ; Cytotoxicity ; Drug Screening Assays, Antitumor ; Enzyme inhibitors ; Female ; Flow cytometry ; Gastric cancer ; High-Throughput Screening Assays ; Humans ; Inhibitors ; kinase target ; Kinases ; Male ; Medical prognosis ; Middle Aged ; Molecular docking ; Molecular Docking Simulation ; Patients ; Polymerase chain reaction ; Prognosis ; Protein Kinase Inhibitors - pharmacology ; Pyrazoles - pharmacology ; Pyridazines - pharmacology ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - enzymology ; Stomach Neoplasms - pathology ; Survival ; Survival Rate ; Tumor cell lines ; Tumors</subject><ispartof>Journal of cellular biochemistry, 2021-10, Vol.122 (10), p.1376-1388</ispartof><rights>2021 Wiley Periodicals LLC</rights><rights>2021 Wiley Periodicals LLC.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3535-607b3a18eb6e0fa3a5d5fb2b7ee2c8b12022eae08fc14657fa9e1be97ca79a9f3</citedby><cites>FETCH-LOGICAL-c3535-607b3a18eb6e0fa3a5d5fb2b7ee2c8b12022eae08fc14657fa9e1be97ca79a9f3</cites><orcidid>0000-0002-6576-0161</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjcb.30015$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjcb.30015$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34160883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mesquita, Felipe P.</creatorcontrib><creatorcontrib>Lucena da Silva, Emerson</creatorcontrib><creatorcontrib>Souza, Pedro F. N.</creatorcontrib><creatorcontrib>Lima, Luina B.</creatorcontrib><creatorcontrib>Amaral, Jackson L.</creatorcontrib><creatorcontrib>Zuercher, William</creatorcontrib><creatorcontrib>Albuquerque, Louise M.</creatorcontrib><creatorcontrib>Rabenhorst, Silvia H. B.</creatorcontrib><creatorcontrib>Moreira‐Nunes, Caroline A.</creatorcontrib><creatorcontrib>Amaral de Moraes, Maria E.</creatorcontrib><creatorcontrib>Montenegro, Raquel C.</creatorcontrib><title>Kinase inhibitor screening reveals aurora‐a kinase is a potential therapeutic and prognostic biomarker of gastric cancer</title><title>Journal of cellular biochemistry</title><addtitle>J Cell Biochem</addtitle><description>Gastric cancer is one of the most common and deadly types of cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric cancer. Here, we explore the antiproliferative and antimigratory effects of the AURKA inhibitor and the prognostic and therapeutic value as a biomarker of gastric cancer. A total of 145 kinase inhibitors were screened to evaluate the cytotoxic or cytostatic effects in the gastric cancer cell line. Using the Alamar Blue assay, flow cytometry, quantitative polymerase chain reaction, and observation of caspase 3/7 activity and cell migration, we investigated the antiproliferative, proapoptotic, and antimigratory effects of the AURKA inhibitor. Moreover, AURKA overexpression was evaluated in the gastric cell lines and the gastric tumor tissue. Out of the 145 inhibitors, two presented the highest antiproliferative effect. Both molecules can induce apoptosis by the caspases 3/7 pathway in addition to inhibiting cancer cell migration, mainly the AURKA inhibitor. Moreover, molecular docking analysis revealed that GW779439X interacts in the active site of the AURKA enzyme with similar energy as a well‐described inhibitor. Our study identified AURKA overexpression in the gastric cancer cell line and gastric tumor tissue, revealing that its overexpression in patients with cancer is correlated with low survival. Therefore, it is feasible to suggest AURKA as a potential marker of gastric cancer, besides providing robust information for diagnosis and estimated survival of patients. AURKA can be considered a new molecular target used in the prognosis and therapy of gastric cancer.
Our study demonstrated the antitumoral effects of Aurora‐A kinase inhibitor against gastric cancer cell line, as well as the overexpression of AURKA gene and its relationship with poor survival of gastric cancer patients</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiproliferatives</subject><subject>Apoptosis</subject><subject>AURKA</subject><subject>Aurora Kinase A - antagonists & inhibitors</subject><subject>Aurora Kinase A - metabolism</subject><subject>biomarker</subject><subject>Biomarkers</subject><subject>Cancer</subject><subject>Caspase-3</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell migration</subject><subject>Cytotoxicity</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Enzyme inhibitors</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Gastric cancer</subject><subject>High-Throughput Screening Assays</subject><subject>Humans</subject><subject>Inhibitors</subject><subject>kinase target</subject><subject>Kinases</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Molecular docking</subject><subject>Molecular Docking Simulation</subject><subject>Patients</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Pyrazoles - pharmacology</subject><subject>Pyridazines - pharmacology</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - enzymology</subject><subject>Stomach Neoplasms - pathology</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Tumor cell lines</subject><subject>Tumors</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10cFu1DAQBmALgejS9sALIEtc4JB2bCdxcqSrQguVemnP0dg72XqbtRc7oSonHoFn5EnqdhcOSD1ZM_r0a6yfsbcCjgSAPF5Zc6QARPWCzQS0uijrsnzJZqAVFFIJucfepLQCgLZV8jXbU6WooWnUjP385jwm4s7fOOPGEHmykcg7v-SRfhAOieMUQ8Q_v34jv93pvOSbMJIfHQ58vKGIG5pGZzn6Bd_EsPQhPY7GhTXGW4o89HyJaYx5adFbigfsVZ_j6XD37rPrz6dX87Pi4vLL-fzTRWFVpaqiBm0UioZMTdCjwmpR9UYaTSRtY4QEKQkJmt6Ksq50jy0JQ622qFtse7XPPmxz81nfJ0pjt3bJ0jCgpzClTlZlWVYt1JDp-__oKkzR5-uy0nUthdIiq49bZWNIKVLfbaLLv7zvBHSPhXS5kO6pkGzf7RIns6bFP_m3gQyOt-DODXT_fFL3dX6yjXwADpSXew</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Mesquita, Felipe P.</creator><creator>Lucena da Silva, Emerson</creator><creator>Souza, Pedro F. 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N. ; Lima, Luina B. ; Amaral, Jackson L. ; Zuercher, William ; Albuquerque, Louise M. ; Rabenhorst, Silvia H. 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N.</au><au>Lima, Luina B.</au><au>Amaral, Jackson L.</au><au>Zuercher, William</au><au>Albuquerque, Louise M.</au><au>Rabenhorst, Silvia H. B.</au><au>Moreira‐Nunes, Caroline A.</au><au>Amaral de Moraes, Maria E.</au><au>Montenegro, Raquel C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kinase inhibitor screening reveals aurora‐a kinase is a potential therapeutic and prognostic biomarker of gastric cancer</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J Cell Biochem</addtitle><date>2021-10</date><risdate>2021</risdate><volume>122</volume><issue>10</issue><spage>1376</spage><epage>1388</epage><pages>1376-1388</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><abstract>Gastric cancer is one of the most common and deadly types of cancer in the world, and poor prognosis with treatment failure is widely reported in the literature. In this context, kinases have been considered a relevant choice for targeted therapy in gastric cancer. Here, we explore the antiproliferative and antimigratory effects of the AURKA inhibitor and the prognostic and therapeutic value as a biomarker of gastric cancer. A total of 145 kinase inhibitors were screened to evaluate the cytotoxic or cytostatic effects in the gastric cancer cell line. Using the Alamar Blue assay, flow cytometry, quantitative polymerase chain reaction, and observation of caspase 3/7 activity and cell migration, we investigated the antiproliferative, proapoptotic, and antimigratory effects of the AURKA inhibitor. Moreover, AURKA overexpression was evaluated in the gastric cell lines and the gastric tumor tissue. Out of the 145 inhibitors, two presented the highest antiproliferative effect. Both molecules can induce apoptosis by the caspases 3/7 pathway in addition to inhibiting cancer cell migration, mainly the AURKA inhibitor. Moreover, molecular docking analysis revealed that GW779439X interacts in the active site of the AURKA enzyme with similar energy as a well‐described inhibitor. Our study identified AURKA overexpression in the gastric cancer cell line and gastric tumor tissue, revealing that its overexpression in patients with cancer is correlated with low survival. Therefore, it is feasible to suggest AURKA as a potential marker of gastric cancer, besides providing robust information for diagnosis and estimated survival of patients. AURKA can be considered a new molecular target used in the prognosis and therapy of gastric cancer.
Our study demonstrated the antitumoral effects of Aurora‐A kinase inhibitor against gastric cancer cell line, as well as the overexpression of AURKA gene and its relationship with poor survival of gastric cancer patients</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34160883</pmid><doi>10.1002/jcb.30015</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6576-0161</orcidid></addata></record> |
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| ispartof | Journal of cellular biochemistry, 2021-10, Vol.122 (10), p.1376-1388 |
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| subjects | Adult Aged Aged, 80 and over Antineoplastic Agents - pharmacology Antiproliferatives Apoptosis AURKA Aurora Kinase A - antagonists & inhibitors Aurora Kinase A - metabolism biomarker Biomarkers Cancer Caspase-3 Cell adhesion & migration Cell Line, Tumor Cell migration Cytotoxicity Drug Screening Assays, Antitumor Enzyme inhibitors Female Flow cytometry Gastric cancer High-Throughput Screening Assays Humans Inhibitors kinase target Kinases Male Medical prognosis Middle Aged Molecular docking Molecular Docking Simulation Patients Polymerase chain reaction Prognosis Protein Kinase Inhibitors - pharmacology Pyrazoles - pharmacology Pyridazines - pharmacology Stomach Neoplasms - drug therapy Stomach Neoplasms - enzymology Stomach Neoplasms - pathology Survival Survival Rate Tumor cell lines Tumors |
| title | Kinase inhibitor screening reveals aurora‐a kinase is a potential therapeutic and prognostic biomarker of gastric cancer |
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