Abstract
Herein, we report the cytotoxicity of cyclopentapeptide analogues of marine natural product galaxamide towards breast carcinoma cells and the underlying mechanisms. We examined the effect of the novel galaxamide analogues on cancer cell proliferation by MTT assay and also further examined the most active compound for morphological changes using Hoechst33342 staining technique, induction of apoptosis, cell cycle phases, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) generation using flow cytometry in human breast cancer MCF-7 cells in vitro. Galaxamide and its analogues effectively induced toxicity in human hepatocellular carcinoma HepG2, human breast carcinoma MCF-7, human epitheloid cervix carcinoma HeLa, and human breast carcinoma MB-MDA-231 cell lines. Amongst them, compound 3 exhibited excellent toxicity towards MCF-7 cells. This galaxamide analogue significantly induced apoptosis in a dose-dependent manner in MCF-7 cells involves cell cycle arrest in the G1 phase, a reduction of MMP, and a marked increase in generation of ROS. Particularly, compound 3 of galaxamide analogues might be a potential candidate for the treatment of breast cancer.
Highlights
Over the past decade, substantial research has demonstrated that oxidative stress plays a crucial role in the development of most chronic diseases including different types of cancer [1]
The solid-phase synthesis method has been developed for the linear pentapeptide using 2-choloro trityl resin
Upon cleavage from solid support with 1% trifluoroacetic acid (TFA) in DCM, linear peptide was obtained in 55–60% overall yield and 95–99% purity which was measured by RP-HPLC
Summary
Substantial research has demonstrated that oxidative stress plays a crucial role in the development of most chronic diseases including different types of cancer [1]. Oxidative stress generated in an excessive amount may introduce gene mutations or affect the intracellular signal transduction and transcription factors, which resulted in an increase of cell proliferation or a reduction of cell apoptosis, leading to carcinogenesis [4, 5]. Breast cancer is the second most common cause of cancer mortality among women worldwide [6]. Breast cancer incidence and death rates generally increase between the ages of 55 and 80. Despite chemotherapeutic treatment of patients with metastatic breast cancer, resistance to therapy and cancer progression have been observed [8]. In this regard, much attention has been paid to active natural compounds for cancer treatment
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