Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription
Abstract Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is steadily rising in developing nations. Cell cycle aberrations due to deregulation of cyclin dependent kinases (CDKs) and cyclins are common events during colorectal carcinogenesis. Herein,...
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Universidade de São Paulo
2025-01-01
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| Series: | Brazilian Journal of Pharmaceutical Sciences |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502025000100333&lng=en&tlng=en |
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| author | Sonal Mohan Manohar Kalpana Sanjay Joshi |
| author_facet | Sonal Mohan Manohar Kalpana Sanjay Joshi |
| author_sort | Sonal Mohan Manohar |
| collection | DOAJ |
| description | Abstract Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is steadily rising in developing nations. Cell cycle aberrations due to deregulation of cyclin dependent kinases (CDKs) and cyclins are common events during colorectal carcinogenesis. Herein, we investigate the anticancer potential of two multitarget CDK inhibitors viz. roscovitine (specific inhibitor of CDK1, 2, 7, and 9) and UCN-01 (pan CDK inhibitor) against three CRC cell lines. Both the drugs exerted cytotoxicity and inhibited clonogenic potential of human CRC cell lines. These drugs induced apoptosis, downregulated cell cycle regulatory and transcriptional CDKs and cyclins’ protein expression as well as their activity. Moreover, dual combination of either of these CDK inhibitors with standard chemotherapeutic drugs was found to be synergistic in CRC cells. Thus, we demonstrate that multiple CDK inhibition offers promising therapeutic strategy against CRC. |
| format | Article |
| id | doaj-art-5f5c3671f22a4bfbb109a71260312859 |
| institution | Kabale University |
| issn | 2175-9790 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Universidade de São Paulo |
| record_format | Article |
| series | Brazilian Journal of Pharmaceutical Sciences |
| spelling | doaj-art-5f5c3671f22a4bfbb109a712603128592025-01-21T07:41:46ZengUniversidade de São PauloBrazilian Journal of Pharmaceutical Sciences2175-97902025-01-016110.1590/s2175-97902025e24402Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcriptionSonal Mohan Manoharhttps://orcid.org/0000-0001-6245-9640Kalpana Sanjay JoshiAbstract Colorectal cancer (CRC) is the third leading cause of cancer death in the world, and its incidence is steadily rising in developing nations. Cell cycle aberrations due to deregulation of cyclin dependent kinases (CDKs) and cyclins are common events during colorectal carcinogenesis. Herein, we investigate the anticancer potential of two multitarget CDK inhibitors viz. roscovitine (specific inhibitor of CDK1, 2, 7, and 9) and UCN-01 (pan CDK inhibitor) against three CRC cell lines. Both the drugs exerted cytotoxicity and inhibited clonogenic potential of human CRC cell lines. These drugs induced apoptosis, downregulated cell cycle regulatory and transcriptional CDKs and cyclins’ protein expression as well as their activity. Moreover, dual combination of either of these CDK inhibitors with standard chemotherapeutic drugs was found to be synergistic in CRC cells. Thus, we demonstrate that multiple CDK inhibition offers promising therapeutic strategy against CRC.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502025000100333&lng=en&tlng=enCDK inhibitorsRoscovitineUCN-01Colorectal cancerCell cycleApoptosisTranscription inhibitionDrug combination |
| spellingShingle | Sonal Mohan Manohar Kalpana Sanjay Joshi Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription Brazilian Journal of Pharmaceutical Sciences CDK inhibitors Roscovitine UCN-01 Colorectal cancer Cell cycle Apoptosis Transcription inhibition Drug combination |
| title | Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription |
| title_full | Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription |
| title_fullStr | Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription |
| title_full_unstemmed | Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription |
| title_short | Multitarget CDK inhibitors roscovitine and UCN‑01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription |
| title_sort | multitarget cdk inhibitors roscovitine and ucn 01 induce apoptosis in colorectal cancer cells by inhibiting cell cycle progression and transcription |
| topic | CDK inhibitors Roscovitine UCN-01 Colorectal cancer Cell cycle Apoptosis Transcription inhibition Drug combination |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502025000100333&lng=en&tlng=en |
| work_keys_str_mv | AT sonalmohanmanohar multitargetcdkinhibitorsroscovitineanducn01induceapoptosisincolorectalcancercellsbyinhibitingcellcycleprogressionandtranscription AT kalpanasanjayjoshi multitargetcdkinhibitorsroscovitineanducn01induceapoptosisincolorectalcancercellsbyinhibitingcellcycleprogressionandtranscription |