Please use this identifier to cite or link to this item: http://hdl.handle.net/2080/3907
Title: Autophagy and NRF2 antioxidant signaling are co-targeted to selectively sensitize cancer stem cells to apoptosis
Authors: Praharaj, Prakash P.
Bhutia, Sujit K.
Keywords: Autophagy
apoptosis
cancer stem cell
NRF2
oral cancer
mtROS
Issue Date: Dec-2022
Citation: International Conference on Recent Advances in Biological Sciences -2022 (RABS-2022), Vikram Deb Autonomous College, Jeypore, Odisha, India, 23-24 December 2022
Abstract: Autophagy affects tumorigenicity and malignancy by regulating cancer stem cell (CSCs) populations. In this study, we demonstrate that cisplatin treatment increases autophagosome formation and speeds up autophagosome-lysosome fusion, thus enriching the CSCs population. An intriguing discovery is that cisplatin treatment boosts autophagic flux by increasing lysosomal activity. In addition, both ATG5 and BECN1 are required for autophagy activation, which is critical for cancer stemness, self-renewal, and cisplatin cytotoxicity in CD44+ cells. Pharmacological inhibition of autophagy (chloroquine; 20 µM; 3 h) increases ROS production, which in turn enhances cisplatin-driven apoptosis in CD44+ CSCs. Further, we showed that cisplatin treatment activates NRF2 (nuclear factor, erythroid 2 like 2) signaling in autophagy-deficient CSCs, which in turn decreases the elevated ROS level and improves cancer stemness. Finally, silencing NRF2 with siNRF2 (a genetic approach) or ML-385 (a pharmacological inhibitor of NRF2) decreased cancer stemness in autophagy-deficient CD44+ cells. Inhibiting autophagy (using CQ) and NRF2 (using ML-385) simultaneously increased cisplatin-induced cytotoxicity and suppressed the expansion of oral CSCs, which may help treat CSC-associated drug resistance and tumor relapse in oral cancer.
Description: Copyright belongs to proceeding publisher
URI: http://hdl.handle.net/2080/3907
Appears in Collections:Conference Papers

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