Licochalcone A Suppresses the Proliferation of Osteosarcoma Cells through Autophagy and ATM-Chk2 Activation
Identifieur interne : 000691 ( Main/Exploration ); précédent : 000690; suivant : 000692Licochalcone A Suppresses the Proliferation of Osteosarcoma Cells through Autophagy and ATM-Chk2 Activation
Auteurs : Tai-Shan Shen [Taïwan] ; Yung-Ken Hsu [Taïwan] ; Yi-Fu Huang [Taïwan] ; Hsuan-Ying Chen [Taïwan] ; Cheng-Pu Hsieh [Taïwan] ; Chiu-Liang Chen [Taïwan]Source :
- Molecules [ 1420-3049 ] ; 2019.
Abstract
Licochalcone A, a flavonoid extracted from licorice root, has been shown to exhibit broad anti-inflammatory, anti-bacterial, anticancer, and antioxidative bioactivity. In this study, we investigated the antitumor activity of Licochalcone A against human osteosarcoma cell lines. The data showed that Licochalcone A significantly suppressed cell viability in MTT assay and colony formation assay in osteosarcoma cell lines. Exposure to Licochalcone A blocked cell cycle progression at the G2/M transition and induced extrinsic apoptotic pathway in osteosarcoma cell lines. Furthermore, we found the Licochalcone A exposure resulted in rapid ATM and Chk2 activation, and high levels of nuclear foci of phosphorylated Chk2 at Thr 68 site in osteosarcoma cell lines. In addition, Licochalcone A exposure significantly induced autophagy in osteosarcoma cell lines. When Licochalcone A-induced autophagy was blocked by the autophagy inhibitor chloroquine, the expression of activated caspase-3 and Annexin V positive cells were reduced, and cell viability was rescued in Licochalcone A-treated osteosarcoma cell lines. These data indicate that the activation of ATM-Chk2 checkpoint pathway and autophagy may contribute to Licochalcone A-induced anti-proliferating effect in osteosarcoma cell lines. Our findings display the possibility that Licochalcone A may serve as a potential therapeutic agent against osteosarcoma.
Url:
DOI: 10.3390/molecules24132435
PubMed: 31269698
PubMed Central: 6651087
Affiliations:
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Hsu</name><affiliation wicri:level="1"><nlm:aff id="af1-molecules-24-02435">Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50006</wicri:regionArea><wicri:noRegion>Changhua 50006</wicri:noRegion></affiliation></author><author><name sortKey="Huang, Yi Fu" sort="Huang, Yi Fu" uniqKey="Huang Y" first="Yi-Fu" last="Huang">Yi-Fu Huang</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02435">Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital, Changhua 50006, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital, Changhua 50006</wicri:regionArea><wicri:noRegion>Changhua 50006</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Hsuan Ying" sort="Chen, Hsuan Ying" uniqKey="Chen H" first="Hsuan-Ying" last="Chen">Hsuan-Ying Chen</name><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02435">Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital, Changhua 50006, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital, Changhua 50006</wicri:regionArea><wicri:noRegion>Changhua 50006</wicri:noRegion></affiliation></author><author><name sortKey="Hsieh, Cheng Pu" sort="Hsieh, Cheng Pu" uniqKey="Hsieh C" first="Cheng-Pu" last="Hsieh">Cheng-Pu Hsieh</name><affiliation wicri:level="1"><nlm:aff id="af1-molecules-24-02435">Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50006</wicri:regionArea><wicri:noRegion>Changhua 50006</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af2-molecules-24-02435">Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital, Changhua 50006, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Orthopedics & Sports Medicine Laboratory, Changhua Christian Hospital, Changhua 50006</wicri:regionArea><wicri:noRegion>Changhua 50006</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Chiu Liang" sort="Chen, Chiu Liang" uniqKey="Chen C" first="Chiu-Liang" last="Chen">Chiu-Liang Chen</name><affiliation wicri:level="1"><nlm:aff id="af1-molecules-24-02435">Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50006, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Orthopedic Surgery, Changhua Christian Hospital, Changhua 50006</wicri:regionArea><wicri:noRegion>Changhua 50006</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-molecules-24-02435">Department of Nursing, Da Yeh University, Changhua 51591, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Nursing, Da Yeh University, Changhua 51591</wicri:regionArea><wicri:noRegion>Changhua 51591</wicri:noRegion></affiliation></author></analytic><series><title level="j">Molecules</title><idno type="eISSN">1420-3049</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Licochalcone A, a flavonoid extracted from licorice root, has been shown to exhibit broad anti-inflammatory, anti-bacterial, anticancer, and antioxidative bioactivity. In this study, we investigated the antitumor activity of Licochalcone A against human osteosarcoma cell lines. The data showed that Licochalcone A significantly suppressed cell viability in MTT assay and colony formation assay in osteosarcoma cell lines. Exposure to Licochalcone A blocked cell cycle progression at the G2/M transition and induced extrinsic apoptotic pathway in osteosarcoma cell lines. Furthermore, we found the Licochalcone A exposure resulted in rapid ATM and Chk2 activation, and high levels of nuclear foci of phosphorylated Chk2 at Thr 68 site in osteosarcoma cell lines. In addition, Licochalcone A exposure significantly induced autophagy in osteosarcoma cell lines. When Licochalcone A-induced autophagy was blocked by the autophagy inhibitor chloroquine, the expression of activated caspase-3 and Annexin V positive cells were reduced, and cell viability was rescued in Licochalcone A-treated osteosarcoma cell lines. These data indicate that the activation of ATM-Chk2 checkpoint pathway and autophagy may contribute to Licochalcone A-induced anti-proliferating effect in osteosarcoma cell lines. Our findings display the possibility that Licochalcone A may serve as a potential therapeutic agent against osteosarcoma.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Mirabello, L" uniqKey="Mirabello L">L. Mirabello</name></author><author><name sortKey="Troisi, R J" uniqKey="Troisi R">R.J. Troisi</name></author><author><name sortKey="Savage, S A" uniqKey="Savage S">S.A. Savage</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Otoukesh, B" uniqKey="Otoukesh B">B. Otoukesh</name></author><author><name sortKey="Boddouhi, B" uniqKey="Boddouhi B">B. Boddouhi</name></author><author><name sortKey="Moghtadaei, M" uniqKey="Moghtadaei M">M. Moghtadaei</name></author><author><name sortKey="Kaghazian, P" uniqKey="Kaghazian P">P. 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Frohlich</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Taïwan</li></country></list><tree><country name="Taïwan"><noRegion><name sortKey="Shen, Tai Shan" sort="Shen, Tai Shan" uniqKey="Shen T" first="Tai-Shan" last="Shen">Tai-Shan Shen</name></noRegion><name sortKey="Chen, Chiu Liang" sort="Chen, Chiu Liang" uniqKey="Chen C" first="Chiu-Liang" last="Chen">Chiu-Liang Chen</name><name sortKey="Chen, Chiu Liang" sort="Chen, Chiu Liang" uniqKey="Chen C" first="Chiu-Liang" last="Chen">Chiu-Liang Chen</name><name sortKey="Chen, Hsuan Ying" sort="Chen, Hsuan Ying" uniqKey="Chen H" first="Hsuan-Ying" last="Chen">Hsuan-Ying Chen</name><name sortKey="Hsieh, Cheng Pu" sort="Hsieh, Cheng Pu" uniqKey="Hsieh C" first="Cheng-Pu" last="Hsieh">Cheng-Pu Hsieh</name><name sortKey="Hsieh, Cheng Pu" sort="Hsieh, Cheng Pu" uniqKey="Hsieh C" first="Cheng-Pu" last="Hsieh">Cheng-Pu Hsieh</name><name sortKey="Hsu, Yung Ken" sort="Hsu, Yung Ken" uniqKey="Hsu Y" first="Yung-Ken" last="Hsu">Yung-Ken Hsu</name><name sortKey="Huang, Yi Fu" sort="Huang, Yi Fu" uniqKey="Huang Y" first="Yi-Fu" last="Huang">Yi-Fu Huang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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