Koenimbin, a natural dietary compound of Murraya koenigii (L) Spreng: inhibition of MCF7 breast cancer cells and targeting of derived MCF7 breast cancer stem cells (CD44(+)/CD24(-/low)): an in vitro study

• Published in: Drug design, development and therapy development and therapy, 2015, Vol.9, p.1193-1208
• Main Authors: Ahmadipour, Fatemeh, Noordin, Mohamed Ibrahim, Mohan, Syam, Arya, Aditya, Paydar, Mohammadjavad, Looi, Chung Yeng, Keong, Yeap Swee, Siyamak, Ebrahimi Nigjeh, Fani, Somayeh, Firoozi, Maryam, Yong, Chung Lip, Sukari, Mohamed Aspollah, Kamalidehghan, Behnam
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis - drug effects; Biological Products - chemistry; Biological Products - isolation & purification; Biological Products - pharmacology; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carbazoles - chemistry; Carbazoles - isolation & purification; Carbazoles - pharmacology; CD24 Antigen - analysis; CD24 Antigen - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Hyaluronan Receptors - analysis; Hyaluronan Receptors - metabolism; MCF-7 Cells; Murraya - chemistry; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Structure-Activity Relationship; Tumor Cells, Cultured
• ISSN: 1177-8881
• DOI: 10.2147/DDDT.S72127

Inhibition of breast cancer stem cells has been shown to be an effective therapeutic strategy for cancer prevention. The aims of this work were to evaluate the efficacy of koenimbin, isolated from Murraya koenigii (L) Spreng, in the inhibition of MCF7 breast cancer cells and to target MCF7 breast cancer stem cells through apoptosis in vitro. Koenimbin-induced cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Nuclear condensation, cell permeability, mitochondrial membrane potential, and cytochrome c release were observed using high-content screening. Cell cycle arrest was examined using flow cytometry, while human apoptosis proteome profiler assays were used to investigate the mechanism of apoptosis. Protein expression levels of Bax, Bcl2, and heat shock protein 70 were confirmed using Western blotting. Caspase-7, caspase-8, and caspase-9 levels were measured, and nuclear factor kappa B (NF-κB) activity was assessed using a high-content screening assay. Aldefluor™ and mammosphere formation assays were used to evaluate the effect of koenimbin on MCF7 breast cancer stem cells in vitro. The Wnt/β-catenin signaling pathway was investigated using Western blotting. Koenimbin-induced apoptosis in MCF7 cells was mediated by cell death-transducing signals regulating the mitochondrial membrane potential by downregulating Bcl2 and upregulating Bax, due to cytochrome c release from the mitochondria to the cytosol. Koenimbin induced significant (P