Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage
The cilium is a microtubule-based organelle that plays a pivotal role in embryonic development and maintenance of physiological functions in the human body. In addition to their function as sensors that transduce diverse extracellular signals, including growth factors, fluid flow, and physical force...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-05-01
|
| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224003184 |
| _version_ | 1797249200563421184 |
|---|---|
| author | Juyeon Hong Keun Yeong Kwon Dong Gil Jang Taejoon Kwon Haejin Yoon Tae Joo Park |
| author_facet | Juyeon Hong Keun Yeong Kwon Dong Gil Jang Taejoon Kwon Haejin Yoon Tae Joo Park |
| author_sort | Juyeon Hong |
| collection | DOAJ |
| description | The cilium is a microtubule-based organelle that plays a pivotal role in embryonic development and maintenance of physiological functions in the human body. In addition to their function as sensors that transduce diverse extracellular signals, including growth factors, fluid flow, and physical forces, cilia are intricately involved in cell cycle regulation and preservation of DNA integrity, as their formation and resorption dynamics are tightly linked to cell cycle progression. Recently, several studies have linked defects in specific ciliary proteins to the DNA damage response. However, it remains unclear whether and how primary cilia contribute to cancer development. Mebendazole (MBZ) is an anthelmintic drug with anticancer properties in some cancer cells. MBZ is continuously being tested for clinical studies, but the precise mechanism of its anticancer activities remains unknown. Here, using Xenopus laevis embryos as a model system, we discovered that MBZ significantly hinders cilia formation and induces DNA damage. Remarkably, primary cilium-bearing cancer cells exhibited heightened vulnerability to combined treatment with MBZ and conventional anticancer drugs. Our findings shed light on the specific influence of MBZ on cilia, rather than cytosolic microtubules, in triggering DNA damage, elucidating a previously unidentified mechanism underlying potential MBZ-mediated cancer therapy. |
| first_indexed | 2024-04-24T20:26:42Z |
| format | Article |
| id | doaj.art-38b44eef5a1d49ceaec7c544743983f7 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-24T20:26:42Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-38b44eef5a1d49ceaec7c544743983f72024-03-22T05:38:43ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-05-01174116434Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damageJuyeon Hong0Keun Yeong Kwon1Dong Gil Jang2Taejoon Kwon3Haejin Yoon4Tae Joo Park5Department of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of KoreaDepartment of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of KoreaDepartment of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of KoreaDepartment of Biological Medical Engineering, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of KoreaDepartment of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of KoreaDepartment of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea; Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea; Corresponding author at: Department of Biological Sciences, College of Information-Bio Convergence Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.The cilium is a microtubule-based organelle that plays a pivotal role in embryonic development and maintenance of physiological functions in the human body. In addition to their function as sensors that transduce diverse extracellular signals, including growth factors, fluid flow, and physical forces, cilia are intricately involved in cell cycle regulation and preservation of DNA integrity, as their formation and resorption dynamics are tightly linked to cell cycle progression. Recently, several studies have linked defects in specific ciliary proteins to the DNA damage response. However, it remains unclear whether and how primary cilia contribute to cancer development. Mebendazole (MBZ) is an anthelmintic drug with anticancer properties in some cancer cells. MBZ is continuously being tested for clinical studies, but the precise mechanism of its anticancer activities remains unknown. Here, using Xenopus laevis embryos as a model system, we discovered that MBZ significantly hinders cilia formation and induces DNA damage. Remarkably, primary cilium-bearing cancer cells exhibited heightened vulnerability to combined treatment with MBZ and conventional anticancer drugs. Our findings shed light on the specific influence of MBZ on cilia, rather than cytosolic microtubules, in triggering DNA damage, elucidating a previously unidentified mechanism underlying potential MBZ-mediated cancer therapy.http://www.sciencedirect.com/science/article/pii/S0753332224003184Primary ciliaCancerMebendazoleDNA damage |
| spellingShingle | Juyeon Hong Keun Yeong Kwon Dong Gil Jang Taejoon Kwon Haejin Yoon Tae Joo Park Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage Biomedicine & Pharmacotherapy Primary cilia Cancer Mebendazole DNA damage |
| title | Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage |
| title_full | Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage |
| title_fullStr | Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage |
| title_full_unstemmed | Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage |
| title_short | Mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting DNA damage |
| title_sort | mebendazole preferentially inhibits cilia formation and exerts anticancer activity by synergistically augmenting dna damage |
| topic | Primary cilia Cancer Mebendazole DNA damage |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224003184 |
| work_keys_str_mv | AT juyeonhong mebendazolepreferentiallyinhibitsciliaformationandexertsanticanceractivitybysynergisticallyaugmentingdnadamage AT keunyeongkwon mebendazolepreferentiallyinhibitsciliaformationandexertsanticanceractivitybysynergisticallyaugmentingdnadamage AT donggiljang mebendazolepreferentiallyinhibitsciliaformationandexertsanticanceractivitybysynergisticallyaugmentingdnadamage AT taejoonkwon mebendazolepreferentiallyinhibitsciliaformationandexertsanticanceractivitybysynergisticallyaugmentingdnadamage AT haejinyoon mebendazolepreferentiallyinhibitsciliaformationandexertsanticanceractivitybysynergisticallyaugmentingdnadamage AT taejoopark mebendazolepreferentiallyinhibitsciliaformationandexertsanticanceractivitybysynergisticallyaugmentingdnadamage |