Linifanib induces apoptosis in human ovarian cancer cells via activation of FOXO3 and reactive oxygen species

Chang Min Lee; Jongsung Lee; Mi-Ae Kang; Hee Taek Kim; Jongbok Lee; Kyungmoon Park; Yung-Hun Yang; Kyu Yun Jang; See-Hyoung Park

Arabian Journal of Chemistry (Dec 2022)

Linifanib induces apoptosis in human ovarian cancer cells via activation of FOXO3 and reactive oxygen species

Chang Min Lee,
Jongsung Lee,
Mi-Ae Kang,
Hee Taek Kim,
Jongbok Lee,
Kyungmoon Park,
Yung-Hun Yang,
Kyu Yun Jang,
See-Hyoung Park

Affiliations

Chang Min Lee: Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, South Korea
Jongsung Lee: Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 03063, South Korea
Mi-Ae Kang: Zoonolab Inc., Seoul 04799, South Korea
Hee Taek Kim: Department of Food Science and Technology, Chungnam National University, Daejeon 34134, South Korea
Jongbok Lee: Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, South Korea
Kyungmoon Park: Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, South Korea
Yung-Hun Yang: Department of Biological Engineering, Konkuk University, Seoul 05029, South Korea
Kyu Yun Jang: Department of Pathology, Jeonbuk National University Medical School, Jeonju 54896, South Korea; Research Institute of Clinical Medicine of Jeonbuk National University, Jeonju 54896, South Korea; Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju 54896, South Korea; Corresponding authors at: Department of Pathology, Jeonbuk National University Medical School, Jeonju 54896, South Korea (K.Y. Jang). Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, South Korea (S-H. Park).
See-Hyoung Park: Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, South Korea; Corresponding authors at: Department of Pathology, Jeonbuk National University Medical School, Jeonju 54896, South Korea (K.Y. Jang). Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, South Korea (S-H. Park).

Journal volume & issue: Vol. 15, no. 12
p. 104321

Abstract

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Linifanib is known as an inhibitor of receptor tyrosine kinase. Even though it has been widely recognized as efficient inhibitor of receptor tyrosine kinases, anti-carcinogenic effect has not been investigated enough in ovarian cancer. In this study, we investigated the anti-cancer effect of linifanib on human ovary cancer SKOV3 cells. WST-1, cell counting assay, and observation of morphological changes were performed to evaluate the cytotoxic effect of linifanib in SKOV3 cells. We analyzed SKOV3 cells treated with linifanib using Muse cell analyzer. We focused on investigating the effect of linifanib on DNA damage in nucleus. Additionally, intracellular reactive oxygen species (ROS) level was measured through Muse cell analyzer. Western blotting was performed to evaluate the protein expression level related to apoptosis. We found that linifanib inhibited proliferation of SKOV3 cells. Our results showed that linifanib induced apoptosis in SKOV3 cells. Additionally, linifanib induced DNA damage in SKOV3 cells. We found that intracellular ROS level increased after treatment of linifanib in SKOV3 cells. Interestingly, FOXO3 was transferred from cytosol into nucleus after linifanib treatment. Taken together, our results supported that linifanib inhibited the proliferation of human ovary cancer SKOV3 cells, which suggested that linifanib might have the potential to be developed as drugs for ovarian cancer treatment.

Published in Arabian Journal of Chemistry

ISSN: 1878-5352 (Print)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Chemistry
Website: http://www.journals.elsevier.com/arabian-journal-of-chemistry/

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