8-bromo-7-methoxychrysin suppress stemness of SMMC-7721 cells induced by co-culture of liver cancer stem-like cells with hepatic stellate cells.

Background: Our previous works have demonstrated that 8-bromo-7-methoxychrysin suppressed stemness of human hepatocellular carcinoma (HCC) cell line SMMC-7721 induced by condition medium from hepatic stellate cell line LX-2 that was activated by liver cancer stem-like cells (LCSCs). However, whether and whereby BrMC inhibits the stemness induced by co-culture of LCSCs and LX-2 cells remains to be investigated.

Methods: The second-generation spheres by sphere culture were identified and used as SMMC-7721-and MHCC97H-derived LCSLCs.

Apigenin inhibits HeLa sphere-forming cells through inactivation of casein kinase 2α.

The protein kinase casein kinase 2 (CK2) has been implicated in stem cell maintenance and its aberrant activation has been demonstrated in several types of cancer, including cervical cancer. In the present study, it was demonstrated that the sphere-forming cells (SFCs) of HeLa cell lines exhibited self-renewal capacity, indicating that they possessed the properties of cervical cancer stem-like cells. HeLa-derived SFCs exhibited a higher level of CK2α protein, compared with the parental cells.

7-difluoromethoxyl-5,4'-di-n-octyl genistein inhibits ovarian cancer stem cell characteristics through the downregulation of FOXM1.

7-Difluoromethoxyl-5,4'-di-n-octylgenistein (DFOG) is a novel synthetic genistein analogue that possesses anti-cancer activity in a variety of cancers, including ovarian cancer. The objective of the present study was to investigate whether DFOG inhibits the self-renewal capacity of ovarian cancer stem-like cells (OCSLCs) and to identify its potential mechanism of action. It was found that the sphere-forming cells (SFCs) of the SKOV3 cell line exhibited a self-renewal capacity and high tumorigenicity, indicating that they possessed the properties of ovarian cancer stem cells (OCSCs).

Casticin induces breast cancer cell apoptosis by inhibiting the expression of forkhead box protein M1.

Casticin is an active ingredient derived from Fructus Viticis, a traditional Chinese medicine. This study aimed to investigate the role of forkhead box O3 (FOXO3a) in breast cancer cells and examine the regulatory mechanisms of FOXO3a in response to casticin treatment of the cells by ELISA, flow cytometry, small interfering RNA (siRNA) transfection and western blot analysis. Casticin treatment induced apoptosis and reduced the expression of the transcription factor forkhead box protein M1 (FOXM1).

Inhibition of cell growth by BrMC through inactivation of Akt in HER-2/neu-overexpressing breast cancer cells.

We previously reported that chrysin (ChR) and its analogs induced cell cycle arrest and apoptosis in human estrogen receptor-positive/-negative breast cancer cells. However, it was unknown whether 8-bromo-7-methoxychrysin (BrMC), a novel synthetic ChR analog, inhibited the cell growth of human epidermal growth factor receptor 2 (HER-2)/neu-overexpressing breast cancers. In the present study, it was demonstrated that BrMC preferentially inhibited the cell viability of HER-2/neu-overexpressing MDA-MB-453 and BT-474 cells.

8-bromo-7-methoxychrysin inhibits properties of liver cancer stem cells via downregulation of β-catenin.

Aim: To evaluate whether 8-bromo-7-methoxychrysin (BrMC), a synthetic analogue of chrysin, inhibits the properties of cancer stem cells derived from the human liver cancer MHCC97 cell line and to determine the potential mechanisms.

Methods: CD133(+) cells were sorted from the MHCC97 cell line by magnetic activated cell sorting, and amplified in stem cell-conditioned medium to obtain the enriched CD133(+) sphere forming cells (SFCs). The stem cell properties of CD133(+) SFCs were validated by the tumorsphere formation assay in vitro and the xenograft nude mouse model in vivo, and termed liver cancer stem cells (LCSCs).

8-bromo-5-hydroxy-7-methoxychrysin targeting for inhibition of the properties of liver cancer stem cells by modulation of Twist signaling.

Emerging evidence has suggested that cancer stem cells with expression of surface biomarkers including CD133 and CD44 have more aggressive biological behavior, including epithelial-mesenchymal transition (EMT), which are closely related to invasion. The upregulation and nuclear relocation of the EMT regulator Twist1 have been implicated in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). In this study, we aimed to isolate and characterize a small population of CD133+ cells that existed in the HCC cell line SMMC-7721 by MACS and investigated the possible roles of 8-bromo-7-methoxychrysin (BrMC), a synthetic analogue of chrysin, in inhibiting the properties of CD133+ sphere-forming cells (SFCs) derived from the HCC cell line SMMC-7721, namely liver cancer stem cells (LCSCs).

Casticin induces ovarian cancer cell apoptosis by repressing FoxM1 through the activation of FOXO3a.

Casticin, a polymethoxyflavone, is reported to have anticancer activities. The aim of the present study was to examine the molecular mechanisms by which casticin induces apoptosis in ovarian cancer cells. The human ovarian cancer cell lines SKOV3 and A2780 were cultured .

Casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells.

Objective: To assess if casticin induces caspase-mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells.

Methods: Human non-small-cell lung carcinoma cell lines H460, A549 and H157 were cultured in vitro. The cytotoxic activities were determined using MTT assay.

Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells.

We previously demonstrated that 5,7-dihydroxy-8-nitrochrysin (NOC), a novel synthetic chrysin analog, preferentially inhibits HER-2/neu-overexpressing MDA-MB-453 breast cancer cell growth by inducing apoptosis; however, the precise molecular mechanism was unclear. In this study, we demonstrated that NOC significantly induces apoptosis of MDA-MB-453 cells and that this is primarily mediated through a mitochondrial death cascade. This was presented as a loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9.

7-difluoromethoxyl-5,4'-di-n-octylgenistein inhibits growth of gastric cancer cells through downregulating forkhead box M1.

Aim: To investigate whether the 7-difluoromethoxyl-5, 4'-di-n-octylgenistein (DFOG), a novel synthetic genistein analogue, affects the growth of gastric cancer cells and its mechanisms.

Methods: A series of genistein analogues were prepared by difluoromethylation and alkylation, and human gastric cancer cell lines AGS and SGC-7901 cultured in vitro were treated with various concentrations of genistein and genistein analogues. The cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

5-allyl-7-gen-difluoromethoxychrysin enhances TRAIL-induced apoptosis in human lung carcinoma A549 cells.

Background: 5-allyl-7-gen-difluoromethoxychrysin (AFMC) is a novel synthetic analogue of chrysin that has been reported to inhibit proliferation in various cancer cell lines. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent.

Methods: The cytotoxicity of A549 and WI-38 cells were determined using colorimetry.