Liposomal DQ in Combination with Copper Inhibits ARID1A Mutant Ovarian Cancer Growth.

Abstract	Therapeutic strategies for ARID1A-mutant ovarian cancers are limited. Higher basal reactive oxygen species (ROS) and lower basal glutathione (GSH) empower the aggressive proliferation ability and strong metastatic property of OCCCs, indicated by the increased marker of epithelial-mesenchymal transition (EMT) and serving the immunosuppressive microenvironment. However, the aberrant redox homeostasis also empowers the sensitivity of DQ-Lipo/Cu in a mutant cell line. DQ, a carbamodithioic acid derivative, generates dithiocarbamate (DDC) in response to ROS, and the chelation of Cu and DDC further generates ROS and provides a ROS cascade. Besides, quinone methide (QM) released by DQ targets the vulnerability of GSH; this effect, plus the increase of ROS, destroys the redox homeostasis and causes cancer cell death. Also importantly, the formed Cu(DDC)2 is a potent cytotoxic anti-cancer drug that successfully induces immunogenic cell death (ICD). The synergistic effect of EMT regulation and ICD will contribute to managing cancer metastasis and possible drug resistance. In summary, our DQ-Lipo/Cu shows promising inhibitory effects in cancer proliferation, EMT markers, and "heat" the immune response.
Authors	Xuejia Kang, Qi Wang, Siqi Wu, Chuanyu Wang, Manjusha Annaji, Chung-Hui Huang, Jianzhong Shen, Pengyu Chen, R Jayachandra Babu
Journal	Biomolecules (Biomolecules) Vol. 13 Issue 5 (04 25 2023) ISSN: 2218-273X [Electronic] Switzerland
PMID	37238613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
Chemical References	Copper Reactive Oxygen Species Liposomes Antineoplastic Agents Glutathione ARID1A protein, human DNA-Binding Proteins Transcription Factors
Topics	Humans Female Copper (pharmacology) Reactive Oxygen Species (metabolism) Cell Line, Tumor Ovarian Neoplasms (drug therapy, genetics) Liposomes (therapeutic use) Antineoplastic Agents (pharmacology, therapeutic use) Glutathione (metabolism) Tumor Microenvironment DNA-Binding Proteins Transcription Factors (genetics)

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