Evaluation of the Anticancer Effects Exerted by 5-fluorouracil and Heme oxygenase-1 Inhibitor Hybrids in HTC116 Colorectal Cancer Cells

Overview

Journal J Enzyme Inhib Med Chem

Specialty Biochemistry

Date 2024 Apr 18

PMID 38634597

Authors

Loredana Salerno

Antonietta Notaro

Valeria Consoli

Federica Affranchi

Valeria Pittala

Valeria Sorrenti

Luca Vanella

Michela Giuliano

Sebastiano Intagliata

Affiliations

Soon will be listed here.

Abstract

Colon cancer remains a clinical challenge in industrialised countries. Its treatment with 5-Flurouracil (5-FU) develops many side effects and resistance. Thus, several strategies have been undertaken so far, including the use of drug cocktails and polypharmacology. Heme oxygenase-1 (HO-1) is an emerging molecular target in the treatment of various cancers. We recently demonstrated that a combination of HO-1 inhibitors with 5-FU and the corresponding hybrids SI1/17, SI1/20, and SI1/22, possessed anticancer activity against prostate and lung cancer cells. In this work, we evaluated these hybrids in a model of colon cancer and found that SI1/22 and the respective combo have greater potency than 5-FU. Particularly, compounds inhibit HO-1 activity in cell lysates, increase ROS and the expression of HO-1, SOD, and Nrf2. Moreover, we observed a decrease of pro-caspase and an increase in cleaved PARP-1 and p62, suggesting apoptotic and autophagic cell death and potential application of these drugs as anticancer agents.

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