Cytotoxicity Study of Cyclopentapeptide Analogues of Marine Natural Product Galaxamide towards Human Breast Cancer Cells

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.

Cyclic Peptides for the Treatment of Cancers: A Review

“…and Phakellia costata [ 27 ]. Cyclic peptides obtained from algae are galaxamide compounds isolated from the marine algae Galaxaura filamentosa [ 28 ]. In addition to these naturally derived cyclic peptides, many more have been chemically synthesized: one example is bacillistatin [ 29 ].…”

Natural Cyclopeptides as Anticancer Agents in the Last 20 Years

“…Galaxamide ( 72) was a representative algae-derived cyclic pentapeptide discovered in marine algae Galaxaura filamentosa, which showed moderate inhibitory activities against Galaxamide ( 72) was a representative algae-derived cyclic pentapeptide discovered in marine algae Galaxaura filamentosa, which showed moderate inhibitory activities against GRC-1 (human renal cell carcinoma, IC 50 = 7.18 µM) and HepG2 (IC 50 = 7.81 µM) cell lines [119]. In the study of Lunagariya et al [120], they investigated the mechanism of action of galaxamide on MCF7 cells in detail. Their results demonstrated that galaxamide induced apoptosis via the oxidative stress-mediated signaling pathway, by which the mitochondrial membrane potential was disrupted in response to the overwhelmed production of reactive oxygen species (ROS).…”

Anti-Cancer Activity of Gabapentin and Chiral Amino Acids-Based Hybrid-Peptides against MCF-7 Breast Cancer Cell-Line

“…The deprotected hydrochloride salt of compound 5 was accomplished by dissolved it (5) in DCM followed by acidification with cold HCl and then stirring for 3-4 hours at room temperature. The diverse targeted motif, i.e., Tripeptide (7), was formed by coupling KSM-2 and6 (HCl salt) in the presence of EDC-HCl and DMAP at RT.…”

“…Despite the intensive investigation of breast cancer cell lines, the cellular and molecular mechanisms between the MCF-7 cell line and the drug polyoxometalate (POM) are still limited [6]. Anticancer peptides (ACPs) have been proved to be effective small molecules (nearly 50 amino acids) that can act specifically against cancerous cells by either a membranolytic mechanism or disruption of mitochondria [7].…”