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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.1
- 수록면
- 227 - 232 (6page)
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Callyspongiolide is a marine macrolide known to induce caspaseindependent cancer cell death. While its toxic effects have been known, the mechanism leading to cell death is yet to be identified. We report that Callyspongiolide R form at C-21 (cally2R) causes mitochondrial dysfunction by inhibiting mitochondrial complex I or II, leading to a disruption of mitochondrial membrane potential and a deprivation of cellular energy. Subsequently, we observed, using electron microscopy, a drastic formation of autophagosome and mitophagy. Supporting these data, LC3, an autophagosome marker, was shown to co-localize with LAMP2, a lysosomal protein, showing autolysosome formation. RNA sequencing results indicated the induction of hypoxia and blocking of EGF-dependent pathways, which could be caused by induction of autophagy. Furthermore, mTOR and AKT pathways preventing autophagy were repressed while AMPK was upregulated, supporting autophagosome progress. Finally, the combination of cally2R with known anti-cancer drugs, such as gefitinib, sorafenib, and rapamycin, led to synergistic cell death, implicating potential therapeutic applications of callyspongiolide for future treatments.
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참고문헌 (23)
참고문헌 신청
Linder B / 2019 / Autophagy in cancer cell death / Biology(Basel) 8:82
Akkoc Y / 2018 / Autophagy and liver cancer / Turk J Gastroenterol 29:270~282
Kim SY / 2021 / Coptisine induces autophagic cell death through down-regulation of PI3K/Akt/mTOR signaling pathway and up-regulation of ROS-mediated mitochondrial dysfunction in hepatocellular carcinoma Hep3B cells / Arch Biochem Biophys 697:108688
Sanchez-Alvarez M / 2019 / Sestrins as a therapeutic bridge between ROS and autophagy in cancer / Cancers(Basel) 11:1415
Bao J / 2020 / The prospects of therapeutic potential and drug development targeting autophagy in cancer / Adv Exp Med Biol 1207:663~679
Akkoc Y / 2018 / Autophagy and liver cancer / Turk J Gastroenterol 29:270~282
Kim SY / 2021 / Coptisine induces autophagic cell death through down-regulation of PI3K/Akt/mTOR signaling pathway and up-regulation of ROS-mediated mitochondrial dysfunction in hepatocellular carcinoma Hep3B cells / Arch Biochem Biophys 697:108688
Sanchez-Alvarez M / 2019 / Sestrins as a therapeutic bridge between ROS and autophagy in cancer / Cancers(Basel) 11:1415
Bao J / 2020 / The prospects of therapeutic potential and drug development targeting autophagy in cancer / Adv Exp Med Biol 1207:663~679
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