Novel Semi-Synthetic Cu (II)-Cardamonin Complex Exerts Potent Anticancer Activity against Triple-Negative Breast and Pancreatic Cancer Cells via Inhibition of the Akt Signaling Pathway

• Published in: Molecules (Basel, Switzerland) Switzerland), 2021-04, Vol.26 (8), p.2166
• Main Authors: Hossan, Md Shahadat, Break, Mohammed Khaled Bin, Bradshaw, Tracey D, Collins, Hilary M, Wiart, Christophe, Khoo, Teng-Jin, Alafnan, Ahmed
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Akt; AKT protein; Antineoplastic Agents - pharmacology; Antitumor activity; Apoptosis; Apoptosis - drug effects; Biological activity; Breast cancer; c-Myc protein; Cancer therapies; cardamonin; Caspase-3; Caspases - metabolism; Cell Cycle Checkpoints - drug effects; Cell Cycle Proteins - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Chalcones - chemistry; Chalcones - pharmacology; Chemical compounds; complex; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Copper - chemistry; Copper - pharmacology; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Cytoskeleton - pathology; Cytotoxicity; DNA Damage; Down-Regulation - drug effects; Histones - metabolism; Humans; Mcl-1 protein; Medical prognosis; Metastasis; Mitosis; Myc protein; Natural products; Pancreatic cancer; Pancreatic Neoplasms - pathology; Pharmacology; Phosphorylation - drug effects; Poly(ADP-ribose) polymerase; Polyphenols; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; Proto-Oncogene Proteins c-myc - metabolism; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal transduction; Signal Transduction - drug effects; Triple Negative Breast Neoplasms - pathology; Tumor cell lines
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules26082166

Cardamonin is a polyphenolic natural product that has been shown to possess cytotoxic activity against a variety of cancer cell lines. We previously reported the semi-synthesis of a novel Cu (II)-cardamonin complex ( ) that demonstrated potent antitumour activity. In this study, we further investigated the bioactivity of against MDA-MB-468 and PANC-1 cancer cells in an attempt to discover an effective treatment for triple-negative breast cancer (TNBC) and pancreatic cancer, respectively. Results revealed that abolished the formation of MDA-MB-468 and PANC-1 colonies, exerted growth-inhibitory activity, and inhibited cancer cell migration. Further mechanistic studies showed that induced DNA damage resulting in gap 2 (G2)/mitosis (M) phase arrest and microtubule network disruption. Moreover, generated reactive oxygen species (ROS) that may contribute to induction of apoptosis, corroborated by activation of caspase-3/7, PARP cleavage, and downregulation of Mcl-1. Complex also decreased the expression levels of p-Akt and p-4EBP1, which indicates that the compound exerts its activity, at least in part, via inhibition of Akt signalling. Furthermore, decreased the expression of c-Myc in PANC-1 cells only, which suggests that it may exert its bioactivity via multiple mechanisms of action. These results demonstrate the potential of as a therapeutic agent for TNBC and pancreatic cancer.