title: Nitidine chloride induces apoptosis, cell cycle arrest, and synergistic cytotoxicity with doxorubicin in breast cancer cells.
abstract: Medicinal plant extracts have been widely used for cancer treatment. Nitidine chloride (NC) is a natural bioactive alkaloid that has recently been reported to have diverse anticancer properties. We aimed to investigate the cytotoxic effects of NC and the effectiveness of combinatorial treatment including NC and doxorubicin in breast cancer cells. Using MTT and flowcytometry assays, we found that NC induced cell growth inhibition and G2/M cell cycle arrest in a time- and dose-dependent manner both in MCF-7 and MDA-MB-231 breast cancer cell lines. Cancer cell growth inhibition was associated with increased levels of the p53 and p21 proteins. Apoptosis induction by NC treatment was confirmed by JC-1 mitochondrial membrane potential, annexin V-positive cell, and TUNEL staining. Using western blot analysis, we found that NC upregulated the pro-apoptotic proteins Bax, cleaved caspase-9 and -3 and cleaved PARP and that it downregulated the anti-apoptotic proteins Bcl-2 and PARP. By using the PI3K/Akt inhibitor LY294002, we further demonstrated that NC-induced apoptosis might be Akt-specific or dependent. In addition, NC exhibited a synergistic effect with doxorubicin on the growth inhibition of the human breast cancer cell lines MCF-7 and MDA-MB-231. Our study demonstrated the anticancer effect of NC on breast cancer and highlighted the potential clinical application of NC.
authors.affiliation: Department of Breast Surgery, Qilu Hospital, Shandong University, Wenhua Xi Road No. 107, Ji'nan, Shandong, 250012, China.
authors.forename: Mingjuan
authors.initials: M
authors.lastname: Sun
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Cai
authors.forename: Jinjing
authors.initials: J
authors.lastname: Cun
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.forename: Shangge
authors.initials: S
authors.lastname: Lv
authors.forename: Qifeng
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053119:Benzophenanthridines / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053119:Benzophenanthridines; D004317:Doxorubicin; C013615:nitidine