title: Chalcone-Coumarin derivatives as potential anti-cancer drugs: an in vitro and in vivo investigation.
abstract: Cancer cells display an overproduction of reactive oxygen species resulting from an exaggerated intrinsic oxidative stress. However, the concept of deleterious oxidants versus beneficial antioxidants has recently evolved. Indeed, molecules like natural coumarins have shown anti-oxidant or pro-oxidant properties depending on their intracellular concentration. Therefore, we have investigated the structure-activity relationship of a variety of coumarin derivatives in terms of cytotoxicity towards human and murine carcinoma cell lines (HT29, HepG2, A549, MCF7, OVCAR and CT26). Amongst those compounds, (E)-7-methoxy-4-(3-oxo-3- phenylprop-1-enyl)-2H-chromen-2-one and (E)-7-hydroxy-4-(3-(4-hydroxyphenyl)-3-oxoprop-1-enyl)-2H-chromen-2-one displayed the most potent cytotoxic effect on colon cancer cells, CT26, (IC50=4.9µM) linked to their pro-oxidant properties. Those compounds triggered the in vitro production of reactive oxygen species by tumor cells, leading to their death through a necrotic process. In vivo, molecules also slowed down tumor growth by 65.7% and 35.4%, respectively, without inducing significant side effects.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jamier
authors.forename: Wioleta
authors.initials: W
authors.lastname: Marut
authors.forename: Sergio
authors.initials: S
authors.lastname: Valente
authors.forename: Christiane
authors.initials: C
authors.lastname: Chereau
authors.forename: Sandrine
authors.initials: S
authors.lastname: Chouzenoux
authors.forename: Carole
authors.initials: C
authors.lastname: Nicco
authors.forename: Herve
authors.initials: H
authors.lastname: Lemarechal
authors.forename: Bernard
authors.initials: B
authors.lastname: Weill
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kirsch
authors.forename: Claus
authors.initials: C
authors.lastname: Jacob
authors.affiliation: Laboratoire d'Immunologie, 24 rue du faubourg St Jacques 75679 Paris cedex 14, France. frederic.batteux@cch.aphp.fr.
authors.forename: Frederic
authors.initials: F
authors.lastname: Batteux
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D064593:Heterografts; D006801:Humans; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008807:Mice, Inbred BALB C; D009336:Necrosis; D009368:Neoplasm Transplantation; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000598187:7-hydroxy-4-(3-(4-hydroxyphenyl)-3-oxoprop-1-enyl)-2H-chromen-2-one; C000598186:7-methoxy-4-(3-oxo-3-phenylprop-1-enyl)-2H-chromen-2-one; D000970:Antineoplastic Agents; D047188:Chalcones; D003374:Coumarins; D017382:Reactive Oxygen Species