Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, fi...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-12-01
|
| Series: | Antibiotics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-6382/11/12/1845 |
| _version_ | 1797461804368003072 |
|---|---|
| author | Anchalee Rawangkan Pattama Wongsirisin Grissana Pook-In Achiraya Siriphap Atchariya Yosboonruang Anong Kiddee Jureeporn Chuerduangphui Nanthawan Reukngam Acharaporn Duangjai Surasak Saokaew Ratsada Praphasawat |
| author_facet | Anchalee Rawangkan Pattama Wongsirisin Grissana Pook-In Achiraya Siriphap Atchariya Yosboonruang Anong Kiddee Jureeporn Chuerduangphui Nanthawan Reukngam Acharaporn Duangjai Surasak Saokaew Ratsada Praphasawat |
| author_sort | Anchalee Rawangkan |
| collection | DOAJ |
| description | Lung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1–1 µM of dinactin suppresses cell growth through induction of the G<sub>0</sub>/G<sub>1</sub> phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., <i>ALDH1A1</i>, <i>Nanog</i>, <i>Oct4</i>, and <i>Sox2</i>) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs. |
| first_indexed | 2024-03-09T17:24:34Z |
| format | Article |
| id | doaj.art-f49c17e7104f462b9b5d269d0a80369d |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T17:24:34Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-f49c17e7104f462b9b5d269d0a80369d2023-11-24T12:55:24ZengMDPI AGAntibiotics2079-63822022-12-011112184510.3390/antibiotics11121845Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung CancerAnchalee Rawangkan0Pattama Wongsirisin1Grissana Pook-In2Achiraya Siriphap3Atchariya Yosboonruang4Anong Kiddee5Jureeporn Chuerduangphui6Nanthawan Reukngam7Acharaporn Duangjai8Surasak Saokaew9Ratsada Praphasawat10Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandDepartment of Medical Services, National Cancer Institute, Bangkok 10400, ThailandDivision of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandDivision of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandDivision of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandDivision of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandDepartment of Microbiology, Faculty of Science, Kasetsart University, Bangkok 10900, ThailandLaboratory of Organic Synthesis, Chulabhorn Research Institute, Bangkok 10210, ThailandDivision of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, ThailandUNIt of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, ThailandDepartment of Pathology, School of Medicine, University of Phayao, Phayao 56000, ThailandLung cancer, especially non-small cell lung cancer (NSCLC), is one of the most complex diseases, despite the existence of effective treatments such as chemotherapy and immunotherapy. Since cancer stem cells (CSCs) are responsible for chemo- and radio-resistance, metastasis, and cancer recurrence, finding new therapeutic targets for CSCs is critical. Dinactin is a natural secondary metabolite produced by microorganisms. Recently, dinactin has been revealed as a promising antitumor antibiotic via various mechanisms. However, the evidence relating to cell cycle progression regulation is constrained, and effects on cancer stemness have not been elucidated. Therefore, the aim of this study is to evaluate the new function of dinactin in anti-NSCLC proliferation, focusing on cell cycle progression and cancer stemness properties in Lu99 and A549 cells. Flow cytometry and immunoblotting analyses revealed that 0.1–1 µM of dinactin suppresses cell growth through induction of the G<sub>0</sub>/G<sub>1</sub> phase associated with down-regulation of cyclins A, B, and D3, and cdk2 protein expression. The tumor-sphere forming capacity was used to assess the effect of dinactin on the cancer stemness potential in NSCLC cells. At a concentration of 1 nM, dinactin reduced both the number and size of the tumor-spheres. The quantitative RT-PCR analyses indicated that dinactin suppressed sphere formation by significantly reducing expression of CSC markers (i.e., <i>ALDH1A1</i>, <i>Nanog</i>, <i>Oct4</i>, and <i>Sox2</i>) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs.https://www.mdpi.com/2079-6382/11/12/1845antitumor antibioticcell cycle arrestCSCdinactinNSCLCstemness |
| spellingShingle | Anchalee Rawangkan Pattama Wongsirisin Grissana Pook-In Achiraya Siriphap Atchariya Yosboonruang Anong Kiddee Jureeporn Chuerduangphui Nanthawan Reukngam Acharaporn Duangjai Surasak Saokaew Ratsada Praphasawat Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer Antibiotics antitumor antibiotic cell cycle arrest CSC dinactin NSCLC stemness |
| title | Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer |
| title_full | Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer |
| title_fullStr | Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer |
| title_full_unstemmed | Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer |
| title_short | Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer |
| title_sort | dinactin a new antitumor antibiotic with cell cycle progression and cancer stemness inhibiting activities in lung cancer |
| topic | antitumor antibiotic cell cycle arrest CSC dinactin NSCLC stemness |
| url | https://www.mdpi.com/2079-6382/11/12/1845 |
| work_keys_str_mv | AT anchaleerawangkan dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT pattamawongsirisin dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT grissanapookin dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT achirayasiriphap dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT atchariyayosboonruang dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT anongkiddee dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT jureepornchuerduangphui dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT nanthawanreukngam dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT acharapornduangjai dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT surasaksaokaew dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer AT ratsadapraphasawat dinactinanewantitumorantibioticwithcellcycleprogressionandcancerstemnessinhibitingactivitiesinlungcancer |