An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer
Abstract Lung cancer is the second most commonly reported type of cancer worldwide. Approximately 80–85% of lung cancer occurrences are accounted by non-small cell lung cancer (NSCLC). Polo-like kinase-1 (Plk1) plays multiple roles in cell cycle progression and its overexpression is observed in majo...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2022-10-01
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| Series: | Journal of Analytical Science and Technology |
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| Online Access: | https://doi.org/10.1186/s40543-022-00345-2 |
| _version_ | 1811238740872396800 |
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| author | Pethaiah Gunasekaran Gong-Hyeon Lee Yeon Sil Hwang Bon-Chul Koo Eun Hee Han Guel Bang Yeo Kyung La Sunghyun Park Hak Nam Kim Mi-Hyun Kim Jeong Kyu Bang Eun Kyoung Ryu |
| author_facet | Pethaiah Gunasekaran Gong-Hyeon Lee Yeon Sil Hwang Bon-Chul Koo Eun Hee Han Guel Bang Yeo Kyung La Sunghyun Park Hak Nam Kim Mi-Hyun Kim Jeong Kyu Bang Eun Kyoung Ryu |
| author_sort | Pethaiah Gunasekaran |
| collection | DOAJ |
| description | Abstract Lung cancer is the second most commonly reported type of cancer worldwide. Approximately 80–85% of lung cancer occurrences are accounted by non-small cell lung cancer (NSCLC). Polo-like kinase-1 (Plk1) plays multiple roles in cell cycle progression and its overexpression is observed in majority of malignancies, including NSCLC. A combination of frontline drugs and inhibitors targeting the Plk kinase domain (KD) has been used to overcome drug resistance in NSCLC. Plk1 KD inhibitors are highly prone to cross-reactivity with similar kinases, eventually leading to undesirable side effects. Moreover, there have been no reports of Plk1 PBD inhibitors showing antitumorigenic effects on NSCLC cells or animal models so far. To address this issue herein, for the first time, our recently reported Plk1 PBD inhibitor KBJK557 was evaluated for the anticancer potential against NSCLC cells. KBJK557 displayed notable cytotoxic effects in A549, PC9, and H1975 cells. Mechanistic investigations revealed that KBJK557-treated cells underwent G2/M cell cycle arrest, triggering subsequent apoptosis. In vivo antitumorigenic activity in xenograft mice model demonstrates that KBJK557-treated mice showed a considerable decrease in tumor size, proving the significances of Plk1 in lung cancer. Collectively, this study demonstrates that KBJK557 can serve as a promising drug candidate for treating the lung cancer through Plk1 PBD inhibition. |
| first_indexed | 2024-04-12T12:47:31Z |
| format | Article |
| id | doaj.art-b29a6cf431d5465bbca67c81159ec350 |
| institution | Directory Open Access Journal |
| issn | 2093-3371 |
| language | English |
| last_indexed | 2024-04-12T12:47:31Z |
| publishDate | 2022-10-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Journal of Analytical Science and Technology |
| spelling | doaj.art-b29a6cf431d5465bbca67c81159ec3502022-12-22T03:32:34ZengSpringerOpenJournal of Analytical Science and Technology2093-33712022-10-0113111010.1186/s40543-022-00345-2An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancerPethaiah Gunasekaran0Gong-Hyeon Lee1Yeon Sil Hwang2Bon-Chul Koo3Eun Hee Han4Guel Bang5Yeo Kyung La6Sunghyun Park7Hak Nam Kim8Mi-Hyun Kim9Jeong Kyu Bang10Eun Kyoung Ryu11Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Dandicure IncDivision of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Department of Internal Medicine, Pusan National University School of Medicine and Biomedical Research Institute, Pusan National University HospitalDivision of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI)Abstract Lung cancer is the second most commonly reported type of cancer worldwide. Approximately 80–85% of lung cancer occurrences are accounted by non-small cell lung cancer (NSCLC). Polo-like kinase-1 (Plk1) plays multiple roles in cell cycle progression and its overexpression is observed in majority of malignancies, including NSCLC. A combination of frontline drugs and inhibitors targeting the Plk kinase domain (KD) has been used to overcome drug resistance in NSCLC. Plk1 KD inhibitors are highly prone to cross-reactivity with similar kinases, eventually leading to undesirable side effects. Moreover, there have been no reports of Plk1 PBD inhibitors showing antitumorigenic effects on NSCLC cells or animal models so far. To address this issue herein, for the first time, our recently reported Plk1 PBD inhibitor KBJK557 was evaluated for the anticancer potential against NSCLC cells. KBJK557 displayed notable cytotoxic effects in A549, PC9, and H1975 cells. Mechanistic investigations revealed that KBJK557-treated cells underwent G2/M cell cycle arrest, triggering subsequent apoptosis. In vivo antitumorigenic activity in xenograft mice model demonstrates that KBJK557-treated mice showed a considerable decrease in tumor size, proving the significances of Plk1 in lung cancer. Collectively, this study demonstrates that KBJK557 can serve as a promising drug candidate for treating the lung cancer through Plk1 PBD inhibition.https://doi.org/10.1186/s40543-022-00345-2Lung cancerPolo-like kinase-1Polo box domainKBJK557Inhibitor |
| spellingShingle | Pethaiah Gunasekaran Gong-Hyeon Lee Yeon Sil Hwang Bon-Chul Koo Eun Hee Han Guel Bang Yeo Kyung La Sunghyun Park Hak Nam Kim Mi-Hyun Kim Jeong Kyu Bang Eun Kyoung Ryu An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer Journal of Analytical Science and Technology Lung cancer Polo-like kinase-1 Polo box domain KBJK557 Inhibitor |
| title | An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer |
| title_full | An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer |
| title_fullStr | An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer |
| title_full_unstemmed | An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer |
| title_short | An investigation of Plk1 PBD inhibitor KBJK557 as a tumor growth suppressor in non-small cell lung cancer |
| title_sort | investigation of plk1 pbd inhibitor kbjk557 as a tumor growth suppressor in non small cell lung cancer |
| topic | Lung cancer Polo-like kinase-1 Polo box domain KBJK557 Inhibitor |
| url | https://doi.org/10.1186/s40543-022-00345-2 |
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