Butein induces apoptotic cell death of human cervical cancer cells

Abstract

Butein is a chalcone, a flavonoid that is widely biosynthesized in plants. Butein has been identified to possess varied pharmacological activity and is extractable from traditional Chinese medicinal herbs, therefore applicable for disease treatment. Recently, in vitro and in vivo studies have shown that butein may induce apoptotic cell death in various human cancer cells. In this study we investigated the apoptotic effect of butein and the underlying mechanisms in human cervical cancer cells. Two cell lines, C-33A and SiHa cells, were treated with butein at different dosages for different durations. The effect of butein on cell viability was assessed by MTT assay, which revealed that butein exerted cytotoxicity in both cervical cancer cells in a dose- and time-dependent fashion. Apoptotic pathway-related factors in the butein-treated cervical cancer cells were then examined. JC-1 flow cytometry, cytochrome c assay, and caspase activity assays demonstrated that butein disturbed mitochondrial transmembrane potential, and increased cytosolic cytochrome c levels and caspase activities in both cervical cancer cells. Western blot analysis revealed that butein downregulated anti-apoptotic protein Bcl-xL and led to proteolytic cleavage of poly (ADP-ribose) polymerase. In addition, butein decreased expressions of the inhibitor of apoptosis (IAP) proteins, including X-linked IAP, survivin, and cellular IAP-1. The findings of this study suggest that butein can decrease cervical cancer cell viability via a pro-apoptotic effect, which involves inhibition of the IAP proteins and activation of both extrinsic and intrinsic pro-apoptotic pathways. Therefore, butein may be applicable for cervical cancer treatment.

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

“…On the other hand, the levels of the other members of Bcl-2 protein family have not been significantly changed. In addition, proteins of the inhibitor of apoptosis family (XIAP, cIAP-1, and survivin) have been downregulated in butein-treated cancer cells [ 71 ]. These authors described a similar mechanism of butein action also in ovarian cancer cell lines [ 72 ].…”

An Investigation on the Therapeutic Potential of Butein, A Tretrahydroxychalcone Against Human Oral Squamous Cell Carcinoma

“…Similarly, the preceding reports have also suggested the same activities against different cancer cells such as breast, blood, liver, cervical etc. (Yang et al, 2012;Liao et al, 2018;Tang et al, 2016;Yang et al, 2018). For instance, Yang et al, (2018) reported that butein reduced the viability of cervical cancer cells through a proapoptotic effect by blocking inhibitor of apoptosis (IAP) proteins and activating extrinsic as well as intrinsic proapoptotic cascades.…”

“…(Yang et al, 2012;Liao et al, 2018;Tang et al, 2016;Yang et al, 2018). For instance, Yang et al, (2018) reported that butein reduced the viability of cervical cancer cells through a proapoptotic effect by blocking inhibitor of apoptosis (IAP) proteins and activating extrinsic as well as intrinsic proapoptotic cascades. Further, it inhibited the proliferation and survival of HCC ells effectively (Liao et al, 2018;Zhou et al, 2018).…”

The Potential of Chinese Herbal Medicines in the Treatment of Cervical Cancer

“…36 Induction of apoptosis of human cervical cancer cells by butein has been reported recently. 37 The researchers found that butein disturbed mitochondrial transmembrane potential and caspase activities in C-33A and SiHa cells; moreover, they demonstrated butein’s proapoptotic effect, including inhibition of IAPs and activation of both extrinsic and intrinsic proapoptotic pathways. 37…”