Biochanin-A induces apoptosis and suppresses migration in FaDu human pharynx squamous carcinoma cells

Abstract

The aim of the present study was to investigate biochanin-A-induced anticancer effects and their cellular signaling pathway in FaDu pharyngeal squamous carcinoma cells. Biochanin-A induced cell death through increased cytotoxicity of FaDu cells in a dose- and time-dependent manner. The number of cells with nucleus condensation and the apoptotic population were increased in the FaDu cells stimulated with biochanin-A for 24 h. Furthermore, extrinsic apoptotic factors such as FasL and their downstream target caspase-8 were increased and activated in the FaDu cells treated with biochanin-A in a dose-dependent manner. Moreover, biochanin-A decreased the expression of intrinsic anti-apoptotic factors such as Bcl-2 and Bcl-xL, and increased the level and activation of intrinsic apoptotic factors such as Bad and caspase-9. Finally, biochanin-A induced the activation of caspase-3 and Poly(ADP ribose) polymerase (PARP) in FaDu cells. Our results suggest that biochanin-A-induced apoptosis was mediated by death receptor mediated-extrinsic and mitochondria-dependent intrinsic apoptotic signaling pathways. Biochanin-A also inhibited wound healing migration and proliferation of FaDu cells via the downregulation and inactivation of matrix metalloproteinase-2 and -9 that are mediated by the suppression of p38, mitogen activated protein kinase (MAPK), NF-κB and Akt cellular signaling pathways. Therefore, these data suggest that the biochanin-A may act as a potential chemotherapeutic compound to treat head and neck cancer.

Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A

“…Biochanin A is a natural compound found in Trifolium pratense L and can work as phytoestrogen in some physiological and pathologic process in vivo [3]. Unlike some other phytoestrogen's facilitating roles in gynaecologic cancer, biochanin A has an antitumor effect on pharynx squamous carcinoma, hepatocellular carcinoma, pancreatic cancer, prostate cancer, and colon tumor in addition [1, 2, 5–8]. As a result, biochanin A may inhibit cancer in other mechanisms.…”

“…Recent reports have mentioned that biochanin A can play a role as a protective factor against osteoporosis, cancers, virus infection, and inflammation, based on its estrogen-like effect, which is also classified as phytoestrogen [1–4]. Along with reports of the antitumor effect of phytoestrogens, biochanin A has also been demonstrated to have an antitumor effect on pharynx squamous carcinoma, hepatocellular carcinoma, pancreatic cancer, prostate cancer, and colon malignancy [2, 5–8].…”

Natural isoflavonoids in invasive cancer therapy: From bench to bedside

“…In SK‐Mel‐28 human malignant melanoma cells, Biochanin A inhibits cell migration and invasion through the NF‐κB and MAPK signaling pathways (Xiao et al, 2017). Biochanin A also inhibited cell migration and invasion in FaDu human pharynx squamous carcinoma cells, decreasing MMP‐2 and MMP‐9 secretion, an effect mediated by inhibition in phosphorylation and activation of p38, NF‐κB, and Akt signaling pathways (Cho et al, 2017). Biochanin A also inhibited the phosphorylation and activation of ERK1/2 and Akt in SK‐BR‐3 breast cancer cells that overexpress HER2.…”

Moscatilin Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma Cells via JNK Signaling Pathway

“…A colony formation assay was performed according to a previously described protocol [30]. FaDu cells were cultured at a density of 200 cells/well in six-well culture plates and incubated at 37 • C for 24 h. After incubation, the cultured FaDu cells were treated with 1 and 5 µM dendrophenol or cisplatin for 24 h and then incubated in a culture medium without moscatilin or cisplatin for 14 days.…”