Phenoxodiol inhibits growth of metastatic prostate cancer cells

Abstract

These data demonstrated that Phenoxodiol promotes apoptosis, as determined by PARP-1 degradation, via mitochondrial depolarization and G1/S cell-cycle arrest thereby confirming that it is active against androgen-dependent and independent prostate cancer cells. Although a precise target for Phenoxodiol has not been identified, these data contribute to our understanding of the mechanism by which this drug promotes cell death in prostate cancer cells, and warrants the continued clinical development of Phenoxodiol as a therapeutic for the treatment of metastatic prostate cancer.

The Effects of Combination Treatment Using Phenoxodiol and Docetaxel, and Phenoxodiol and Secreted Frizzled-related Protein 4 on Prostate Cancer Cell Lines

“…As phenoxodiol is able to affect the cell cycle [16,17], a series of experiments were run to determine potential synergy, additivity, interference, or lack of interaction between each compound. Figure 1: Docetaxel response curve measured after 48 hr of treatment.…”

“…Phenoxodiol has exhibited the ability to induce G1/S phase cell cycle arrest, while docetaxel's published method of action is to inhibit the cell cycle at the M phase, resulting in G2 phase arrest [5,16]. After determining the minimum effective concentration dose, an isobologram was performed to look for interaction between phenoxodiol (PXD) and docetaxel (DOC) using varying concentrations of each.…”

“…This was followed by the result that, at both 10 µM and 30 µM concentrations, there was a significant increase in proliferation versus 100 nM docetaxel alone, meaning that phenoxodiol had significantly impacted the ability of docetaxel to induce cell arrest at the G2/M stage. While synergism and additivity are the targets of drugs, especially those with different modes of action, phenoxodiol's exhibited ability to induce cell arrest at G1 and S phases of the cell cycle prevents the cells from entering the G2/M region where docetaxel can be effective [16]. Studies have also indicated that increased expression of p21WAF1 corresponds to an inhibition of docetaxel activity via a p38 dependent signaling pathway, and that cell cycle inhibitors can actually protect the cells from taxane induced cell death during certain periods [4,23].…”

“…We also investigated the use of the novel prostate cancer therapeutic phenoxodiol, which has been shown to affect the cell cycle of carcinogenic prostate cells [16,17]. Potential interactions of phenoxodiol and docetaxel across multiple concentrations are investigated, searching for synergistic, additive, or interference effects.…”

A simple and robust high-performance liquid chromatography coupled to a diode-array detector method for the analysis of genistein in mouse tissues

“…Soy is a very important constituent in Asian and vegetarian nutrition [2], and represents a huge economic impact on society. Additionally, epidemiological studies suggest that GEN helps to protect against cancer [3][4][5][6][7], cardiovascular diseases [8], osteoporosis [9], age-related diseases [10] and inflammation processes [11]. Probably the most attractive activity of this bioflavonoid is its promising chemopreventive activity, which works by inducing either G 2 /M or G 0 /G 1 cell cycle arrest depending on the cell line [12][13][14].…”