Anti-Tumor and Radiosensitization Effects of N-Butylidenephthalide on Human Breast Cancer Cells.

Yi-Ju Su,Kuan-Fu Liao,Sung-Ying Huang,Yu-Hui Ni,Sheng-Chun Chiu

doi:10.3390/molecules23020240

Abstract

N-Butylidenephthalide (BP), which is extracted from a traditional Chinese medicine, Radix Angelica Sinensis (danggui), displays antitumor activity against various cancer cell lines. The purpose of this study was to investigate the cytotoxic and radiosensitizing effect of BP and the underlying mechanism of action in human breast cancer cells. BP induces apoptosis in breast cancer cells, which was revealed by the TUNEL assay; the activation of caspase-9 and PARP was detected by western blot. In addition, BP-induced G2/M arrest was examined by flow cytometry and the expression levels of the G2/M regulatory protein were detected by western blot. BP also suppresses the migration and invasion of breast cancer cells, which was tested by wound healing and the matrigel invasion assay; the involvement of EMT-related gene expressions was detected by real-time PCR. Furthermore, BP enhanced the radiosensitivity of breast cancer cells, which was measured by the colony formation assay and comet assay, where the foci of γ-H2AX after radiation significantly increased in BP pretreated cells and was evidenced by immunocytochemistry staining and western blot. The homologous recombination (HR) repair protein Rad51 was down-regulated after BP pretreatment. These results indicate that BP might be a potential chemotherapeutic and radiosensitizing agent for breast cancer therapy.

Highlights

Breast cancer is the most commonly diagnosed malignancies among women and the leading cause of cancer death in females from Western countries, with an estimated 1.7 million new breast cancer cases and 522,000 deaths worldwide in 2012 [1]
For determining the effect of BP on cell viability, human MDA-MB-231 and MCF-7 breast cancer cell lines were incubated with various concentrations of BP (12.5 to 100 μg/mL) for 24 or 48 h, followed by MTT assay analysis (Figure 1B)
The results showed that BP suppressed the breast cancer cells growth in a time- and dose-dependent manner, the EC50 values at 48 h were 46.7 μg/mL (MDA-MB-231)

Summary

Introduction

Breast cancer is the most commonly diagnosed malignancies among women and the leading cause of cancer death in females from Western countries, with an estimated 1.7 million new breast cancer cases and 522,000 deaths worldwide in 2012 [1]. Treatment options for breast cancer patients are limited to conventional cytotoxic chemotherapy, which is not effective against high-grade malignant tumors [2,3,4]. Molecules 2018, 23, 240 regional control of epithelial carcinomas including breast cancer. Recent attempts have focused on using potential chemotherapeutic chemicals as radiosensitizing agents to enhance the efficacy of radiation therapy. Non-traditional treatments using herbs and dietary supplements have been considered as alternative medicines for cancer therapy. BP represses the transcriptional activity of hTERT via down-regulating the expression of AP-2, leading to the telomerase activity inhibition in lung cancer [7]. BP down-regulates the expression of S-phase kinase-associated protein (Skp2), resulting in cell cycle G0/G1 phase arrest and tumor senescence in glioblastoma multiforms (GBM) [10]. BP reduces the epithelial-mesenchymal transition (EMT) via the modulation of enhancements of Zeste

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