Dinactin: A New Antitumor Antibiotic with Cell Cycle Progression and Cancer Stemness Inhibiting Activities in Lung Cancer
Anchalee Rawangkan,
Pattama Wongsirisin,
Grissana Pook-In,
Achiraya Siriphap,
Atchariya Yosboonruang,
Anong Kiddee,
Jureeporn Chuerduangphui,
Nanthawan Reukngam,
Acharaporn Duangjai,
Surasak Saokaew,
Ratsada Praphasawat
Affiliations
Anchalee Rawangkan
Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
Pattama Wongsirisin
Department of Medical Services, National Cancer Institute, Bangkok 10400, Thailand
Grissana Pook-In
Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
Achiraya Siriphap
Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
Atchariya Yosboonruang
Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
Anong Kiddee
Division of Microbiology and Parasitology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
Jureeporn Chuerduangphui
Department of Microbiology, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand
Nanthawan Reukngam
Laboratory of Organic Synthesis, Chulabhorn Research Institute, Bangkok 10210, Thailand
Acharaporn Duangjai
Division of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand
Surasak Saokaew
UNIt of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao 56000, Thailand
Ratsada Praphasawat
Department of Pathology, School of Medicine, University of Phayao, Phayao 56000, Thailand
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 G0/G1 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., ALDH1A1, Nanog, Oct4, and Sox2) in Lu99 cells. Consequently, dinactin could be a promising strategy for NSCLC therapy targeting CSCs.
