Abstract 4500: Enedione derivates as a potential cancer treatment through the inhibition of COPZ1

Abstract

Cancer is a leading cause of death worldwide; it was responsible for approximately 10 million deaths in 2020. Besides surgery for tumor removal, the most common treatments available are chemotherapy and radiation, which are not selective, resulting in side effects such as pain, hair loss, nausea, and vomiting. They are also ineffective against stem-like and dormant tumor cells, which could lead to a relapse and/or metastasis. Consequently, the development of drugs with tumor-specific targets is needed. COPI is a coatomer responsible for the retrograde transport from Golgi complex (GC) to the endoplasmic reticulum (ER). In this context, we developed four compounds targeting disruption of GC through inhibition of COPI and previous results showed that compounds 1-4 significantly decrease cell viability of pancreatic cancer cell lines MIA PaCa-2 and AsPC-1, compared to hTERT-HPNE normal pancreatic cell line. In the present work, RT q-PCR confirmed that the two isoforms of the COPI ζ subunit COPZ1 and COPZ2 are expressed at similar levels in normal cells while COPZ2 is downregulated in tumor cell lines. Our in vitro results demonstrated that compounds 1-4 decreased cell viability of breast cancer (HCC1143) and melanoma (A-395) cell lines. The tested compounds are able to target COPZ1-dependent tumor cells, therefore they are great candidates for further studies aiming to develop a selective treatment for cancer. Citation Format: Allana C. Martins, Barbara Mitsuyasu Barbosa, Ingridhy O. Maia Freitas da Silveira, Roberto Gomes. Enedione derivates as a potential cancer treatment through the inhibition of COPZ1. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4500.