Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines

<div><p>Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau (VHL) tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmark...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Mazhar Pasha (11197767) (author)
مؤلفون آخرون: Siveen K. Sivaraman (17280685) (author), Ronald Frantz (18134095) (author), Abdelali Agouni (181926) (author), Shankar Munusamy (14590810) (author)
منشور في: 2019
الموضوعات:
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author Mazhar Pasha (11197767)
author2 Siveen K. Sivaraman (17280685)
Ronald Frantz (18134095)
Abdelali Agouni (181926)
Shankar Munusamy (14590810)
author2_role author
author
author
author
author_facet Mazhar Pasha (11197767)
Siveen K. Sivaraman (17280685)
Ronald Frantz (18134095)
Abdelali Agouni (181926)
Shankar Munusamy (14590810)
author_role author
dc.creator.none.fl_str_mv Mazhar Pasha (11197767)
Siveen K. Sivaraman (17280685)
Ronald Frantz (18134095)
Abdelali Agouni (181926)
Shankar Munusamy (14590810)
dc.date.none.fl_str_mv 2019-03-22T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/biom9030113
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Metformin_Induces_Different_Responses_in_Clear_Cell_Renal_Cell_Carcinoma_Caki_Cell_Lines/25378837
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Biochemistry and cell biology
renal cell carcinoma
von Hippel-Lindau
hypoxia-inducible factor
AMP-activated kinase
metformin
dc.title.none.fl_str_mv Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau (VHL) tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmarks of ccRCC. Persistently activated HIF-1α is associated with increased cell proliferation, angiogenesis, and epithelial–mesenchymal transition (EMT), consequently leading to ccRCC progression and metastasis to other organs. However, the VHL status alone cannot predict the differential sensitivity of ccRCC to cancer treatments, which suggests that other molecular differences may contribute to the differential response of ccRCC cells to drug therapies. In this study, we investigated the response to metformin (an antidiabetic drug) of two human ccRCC cell lines Caki-1 and Caki-2, which express wild-type VHL. Our findings demonstrate a differential response between the two ccRCC cell lines studied, with Caki-2 cells being more sensitive to metformin compared to Caki-1 cells, which could be linked to the differential expression of HIF-1 despite both cell lines carrying a wild-type VHL. Our study unveils the therapeutic potential of metformin to inhibit the progression of ccRCC in vitro. Additional preclinical and clinical studies are required to ascertain the therapeutic efficacy of metformin against ccRCC.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biomolecules<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biom9030113" target="_blank">https://dx.doi.org/10.3390/biom9030113</a></p>
eu_rights_str_mv openAccess
id Manara2_fbf2dc3c976d4a8147d91024660d06f7
identifier_str_mv 10.3390/biom9030113
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25378837
publishDate 2019
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rights_invalid_str_mv CC BY 4.0
spelling Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell LinesMazhar Pasha (11197767)Siveen K. Sivaraman (17280685)Ronald Frantz (18134095)Abdelali Agouni (181926)Shankar Munusamy (14590810)Biological sciencesBiochemistry and cell biologyrenal cell carcinomavon Hippel-Lindauhypoxia-inducible factorAMP-activated kinasemetformin<div><p>Clear cell renal cell carcinoma (ccRCC) is the most common and lethal form of urological cancer diagnosed globally. Mutations of the von Hippel-Lindau (VHL) tumor-suppressor gene and the resultant overexpression of hypoxia-inducible factor (HIF)-1α protein are considered hallmarks of ccRCC. Persistently activated HIF-1α is associated with increased cell proliferation, angiogenesis, and epithelial–mesenchymal transition (EMT), consequently leading to ccRCC progression and metastasis to other organs. However, the VHL status alone cannot predict the differential sensitivity of ccRCC to cancer treatments, which suggests that other molecular differences may contribute to the differential response of ccRCC cells to drug therapies. In this study, we investigated the response to metformin (an antidiabetic drug) of two human ccRCC cell lines Caki-1 and Caki-2, which express wild-type VHL. Our findings demonstrate a differential response between the two ccRCC cell lines studied, with Caki-2 cells being more sensitive to metformin compared to Caki-1 cells, which could be linked to the differential expression of HIF-1 despite both cell lines carrying a wild-type VHL. Our study unveils the therapeutic potential of metformin to inhibit the progression of ccRCC in vitro. Additional preclinical and clinical studies are required to ascertain the therapeutic efficacy of metformin against ccRCC.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Biomolecules<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/biom9030113" target="_blank">https://dx.doi.org/10.3390/biom9030113</a></p>2019-03-22T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/biom9030113https://figshare.com/articles/journal_contribution/Metformin_Induces_Different_Responses_in_Clear_Cell_Renal_Cell_Carcinoma_Caki_Cell_Lines/25378837CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/253788372019-03-22T03:00:00Z
spellingShingle Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
Mazhar Pasha (11197767)
Biological sciences
Biochemistry and cell biology
renal cell carcinoma
von Hippel-Lindau
hypoxia-inducible factor
AMP-activated kinase
metformin
status_str publishedVersion
title Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
title_full Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
title_fullStr Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
title_full_unstemmed Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
title_short Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
title_sort Metformin Induces Different Responses in Clear Cell Renal Cell Carcinoma Caki Cell Lines
topic Biological sciences
Biochemistry and cell biology
renal cell carcinoma
von Hippel-Lindau
hypoxia-inducible factor
AMP-activated kinase
metformin