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Article

Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells

1
Department of Animal Science and Biotechnology, ITRD, Kyungpook National University, Sangju 37224, Korea
2
Gyeongbuk Livestock Research Institute, Yeongju 36052, Korea
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School of Life Science, Kyungpook National University, Daegu 41566, Korea
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College of Korean Medicine, Dongshin University, Naju 58245, Korea
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The Pathophysiology Department, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450008, China
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Department of Dental Hygiene, Kyungpook National University, Sangju 37224, Korea
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Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu 41566, Korea
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Department of Bio-Medical Analysis, Korea Polytechnic College, Chungnam 34134, Korea
*
Authors to whom correspondence should be addressed.
Academic Editor: Laura Paleari
Int. J. Mol. Sci. 2021, 22(14), 7509; https://doi.org/10.3390/ijms22147509
Received: 2 June 2021 / Revised: 23 June 2021 / Accepted: 2 July 2021 / Published: 13 July 2021
(This article belongs to the Special Issue Cancer Prevention with Molecular Target Therapies 2.0)
Oral cancer (OC) has been attracted research attention in recent years as result of its high morbidity and mortality. Costunolide (CTD) possesses potential anticancer and bioactive abilities that have been confirmed in several types of cancers. However, its effects on oral cancer remain unclear. This study investigated the potential anticancer ability and underlying mechanisms of CTD in OC in vivo and in vitro. Cell viability and anchorage-independent colony formation assays were performed to examine the antigrowth effects of CTD on OC cells; assessments for migration and invasion of OC cells were conducted by transwell; Cell cycle and apoptosis were investigated by flow cytometry and verified by immunoblotting. The results revealed that CTD suppressed the proliferation, migration and invasion of oral cancer cells effectively and induced cell cycle arrest and apoptosis; regarding the mechanism, CTD bound to AKT directly by binding assay and repressed AKT activities through kinase assay, which thereby downregulating the downstream of AKT. Furthermore, CTD remarkably promotes the generation of reactive oxygen species by flow cytometry assay, leading to cell apoptosis. Notably, CTD strongly suppresses cell-derived xenograft OC tumor growth in an in vivo mouse model. In conclusion, our results suggested that costunolide might prevent progression of OC and promise to be a novel AKT inhibitor. View Full-Text
Keywords: costunolide; ROS; AKT pathway; apoptosis; oral cancer costunolide; ROS; AKT pathway; apoptosis; oral cancer
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Figure 1

MDPI and ACS Style

Huang, H.; Yi, J.-K.; Lim, S.-G.; Park, S.; Zhang, H.; Kim, E.; Jang, S.; Lee, M.-H.; Liu, K.; Kim, K.-R.; Kim, E.-K.; Lee, Y.; Kim, S.-H.; Ryoo, Z.-Y.; Kim, M.O. Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells. Int. J. Mol. Sci. 2021, 22, 7509. https://doi.org/10.3390/ijms22147509

AMA Style

Huang H, Yi J-K, Lim S-G, Park S, Zhang H, Kim E, Jang S, Lee M-H, Liu K, Kim K-R, Kim E-K, Lee Y, Kim S-H, Ryoo Z-Y, Kim MO. Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells. International Journal of Molecular Sciences. 2021; 22(14):7509. https://doi.org/10.3390/ijms22147509

Chicago/Turabian Style

Huang, Hai, Jun-Koo Yi, Su-Geun Lim, Sijun Park, Haibo Zhang, Eungyung Kim, Soyoung Jang, Mee-Hyun Lee, Kangdong Liu, Ki-Rim Kim, Eun-Kyong Kim, Youngkyun Lee, Sung-Hyun Kim, Zae-Young Ryoo, and Myoung O. Kim. 2021. "Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells" International Journal of Molecular Sciences 22, no. 14: 7509. https://doi.org/10.3390/ijms22147509

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