Abstract 4132: Low-dose carbon monoxide therapies suppress cancer metastasis

Abstract

Abstract Metastasis is the primary cause of cancer-related deaths. Novel systemic therapies for metastatic cancer are urgently needed. Carbon monoxide (CO) is an endogenously produced signaling molecule in the human body with demonstrated pharmacological activities, including organ protection and anti-inflammation. We determined the therapeutic effect of low-dose CO and CO prodrugs on cancer progression in this study. We found that low-dose CO inhibits the migration of cancer cell lines including breast, pancreatic, colon, prostate, liver, and lung cancer. We showed that low-dose CO inhibits lung metastasis of breast cancer and liver metastasis of pancreatic cancer in preclinical mouse models. Further, to provide safer and more reliable CO delivery, we developed metal-free, organic CO prodrugs and showed that CO prodrugs inhibit tumor growth and metastasis. We demonstrated that low-dose CO blocks the transcription of heme importers, leading to diminished intracellular heme levels. Altogether, our work lays a strong foundation for the development of CO-based systemic cancer therapies. Citation Format: Tiantian Zhang, Cheryl Zhang, Xiang Chen, Xiaoxiao Yang, Qiyue Mao, George Zhang, Zhengming Chen, Adrian Tan, Jenny Zhaoying Xiang, Erika Hissong, Yao-Tseng Chen, Binghe Wang, Nancy Du. Low-dose carbon monoxide therapies suppress cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4132.