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

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.

Enhancement of cytotoxicity and induction of apoptosis by cationic nano-liposome formulation of n-butylidenephthalide in breast cancer cells

“…Moreover, Bax protein expression increased, which suggested that BP might affect mitochondrial function and lead to the induction of the intrinsic apoptotic pathway. The results revealed that BP induced intrinsic as well as extrinsic apoptosis pathway and was similar to previous research had found in MDA-MB-231 cells [24].…”

“…BP is commonly used in the treatment for some gynecological diseases and is well-known for its anti-cancer ability against several cancer types through cell cycle arrest or cell apoptosis. Moreover, BP has found the anticancer activity in MDA-MB-231 and MCF-7 cells through induction of cell apoptosis, block of cell cycle progression, the contribution of DNA damage and repression of cell migration and invasion in vitro [24]. However, the anti-cancer mechanisms in SK-BR-3 cells remained unclear until our results presented that BP blocked the cell cycle at the G0/G1 phase and induced both intrinsic and extrinsic apoptosis pathways.…”

“…n-Butylidenephthalide (BP), a natural compound extracted from Angelica sinensis [11,12], exhibits various pharmacological activities, such as alleviating liver injury and fibrosis [13], acaricidal activities [14], and neuroprotective activities [15][16][17]. It is widely reported in the literature that BP induces cell cycle arrest or cell apoptosis in various human cancer cell lines in vitro or in vivo, including brain, lung, colon, prostate, breast, and liver cancer [18][19][20][21][22][23][24][25]. BP reduces cell cycle regulators, suppresses the activity of telomerase reverse transcriptase, and activates the Nur77-mediated apoptosis pathway, causing tumor cell apoptosis [26,27].…”

Identification of the metabolites of n‐butylidenephthalide in rat and human liver microsomes by liquid chromatography–high‐resolution mass spectrometry

“…Rhizoma of chuanxiong contains essential oil, of which the main constituents are phthalides including senkyunolide I, ligustilide, n-butylidenephthalide (NBDP; Figure 1) and n-butylphthalide (Beck & Chou, 2007;He, Li, & Bi, 2015;Li et al, 2003). Among these phthalides, NBDP is one of the bioactive components and has been demonstrated to have antitumor activity against various cancer cell lines, including breast cancer, colorectal cancer and glioblastoma (Su, Huang, Ni, Liao, & Chiu, 2018;Tsai et al, 2006Tsai et al, , 2005Wei et al, 2009). In addition to its anti-tumor activity, NBDP has been demonstrated to have protective effects against neurotoxicity through regulating tryptophan 2, 3-dioxygenase and has the potential in the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases (Fu et al, 2014;Rajamani et al, 2017).…”

Special Issue: Natural Products: Anticancer and Beyond

“…6-gingerol, 10-gingerol, 6-shogaol, and 10-shogaol, isolated from ginger, significantly inhibited the proliferation of docetaxel-resistant human prostate cancer cell line PC3R via downregulation of multidrug resistance-associated protein 1 and glutathione-S-transferase protein expression [ 23 ]. N-Butylidenephthalide, an active component of Radix Angelica Sinensis (danggui) , showed potent inhibition and radiosensitization in human MDA-MB-231 and MCF-7 breast cancer cell lines [ 24 ]. These studies indicated that many natural products may work as sensitizing agents for MDR cancer treatment.…”