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

Xuejia Kang; Qi Wang; Siqi Wu; Chuanyu Wang; Manjusha Annaji; Chung-Hui Huang; Jianzhong Shen; Pengyu Chen; R. Jayachandra Babu

doi:10.3390/biom13050744

Biomolecules (Apr 2023)

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

Xuejia Kang,
Qi Wang,
Siqi Wu,
Chuanyu Wang,
Manjusha Annaji,
Chung-Hui Huang,
Jianzhong Shen,
Pengyu Chen,
R. Jayachandra Babu

Affiliations

Xuejia Kang: Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA
Qi Wang: Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA
Siqi Wu: Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA
Chuanyu Wang: Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA
Manjusha Annaji: Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA
Chung-Hui Huang: Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA
Jianzhong Shen: Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA
Pengyu Chen: Materials Research and Education Center, Materials Engineering, Department of Mechanical Engineering, Auburn University, Auburn, AL 36849, USA
R. Jayachandra Babu: Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn, AL 36849, USA

DOI: https://doi.org/10.3390/biom13050744
Journal volume & issue: Vol. 13, no. 5
p. 744

Abstract

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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.

Published in Biomolecules

ISSN: 2218-273X (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: https://www.mdpi.com/journal/biomolecules

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