Role of apoptosis and autophagy in folic acid-induced cytotoxicity of human breast cancer cells in vitro

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Munevver Baran, Gozde Ozge Onder, Ozge Goktepe, Arzu Yay
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Abstract

Obstacles to the successful treatment of breast cancer patients with chemotherapeutic agents can be overcome with effective new strategies. It is still unclear how folic acid affects the onset and spread of breast cancer. The purpose of this study was to determine how folic acid affected the apoptotic and autophagic pathways of the breast cancer cell lines MCF-7 and MDA-MB-231. In the present study, folic acid was applied to MCF-7 and MDA-MB-231 breast cancer cell lines at different concentrations and for different durations. MTT analysis was used to investigate cytotoxic activity. All groups underwent the Tunel staining procedure to identify apoptosis and the immunofluorescence staining approach to identify the autophagic pathway. 24-hour folic acid values were accepted as the most appropriate cytotoxic dose. In MCF-7, cell cycle arrest was observed in the S phase and MDA-MB-231 G1/G0 phases. When apoptotic TUNEL staining was evaluated in both cell lines, folic acid significantly increased apoptosis. While a significant difference was observed between the groups in terms of Beclin 1 immunoreactivity in the MDA-MB-231 cell line, there was no significant difference in the MCF-7 cell line. In addition, statistical significance was not observed LC3 immunoreactivity in both cell lines. In the study, it was observed that folic acid induced autophagy at the initial stage in the MDA-MB-231 cell line but had no inductive effect in the MCF-7 cell line. In conclusion, our findings showed that folic acid has a potential cytotoxic and therapeutic effect on MCF-7 and MDA-MB-231 breast cancer cell lines.

叶酸诱导体外人类乳腺癌细胞凋亡和自噬在细胞毒性中的作用
采用有效的新策略可以克服乳腺癌患者成功接受化疗的障碍。目前还不清楚叶酸如何影响乳腺癌的发病和扩散。本研究旨在确定叶酸如何影响乳腺癌细胞株 MCF-7 和 MDA-MB-231 的凋亡和自噬途径。在本研究中,对 MCF-7 和 MDA-MB-231 乳腺癌细胞株施用了不同浓度和不同持续时间的叶酸。MTT 分析用于研究细胞毒性活性。所有实验组均采用 Tunel 染色法鉴定细胞凋亡,并采用免疫荧光染色法鉴定自噬途径。24小时叶酸值被认为是最合适的细胞毒性剂量。在MCF-7中,细胞周期停滞在S期,在MDA-MB-231中停滞在G1/G0期。在对这两种细胞系的细胞凋亡TUNEL染色进行评估时,叶酸显著增加了细胞凋亡。虽然在 MDA-MB-231 细胞系中观察到各组间的 Beclin 1 免疫活性有明显差异,但在 MCF-7 细胞系中却没有明显差异。此外,在两种细胞系中均未观察到 LC3 免疫反应具有统计学意义。研究观察到,叶酸在 MDA-MB-231 细胞系的初期阶段能诱导自噬,但对 MCF-7 细胞系没有诱导作用。总之,我们的研究结果表明,叶酸对 MCF-7 和 MDA-MB-231 乳腺癌细胞系具有潜在的细胞毒性和治疗作用。
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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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