wogonin and oridonin

The initial response rates of advanced-stage epithelial ovarian cancer to the chemotherapeutic agents carboplatin and paclitaxel are high. However, once drug resistance develops, further chemotherapy is less effective. The objective of this study is to investigate the anti-proliferative activity of the phyto-active chemicals (PACs) oridonin and wogonin in chemo-resistant epithelial ovarian cancer cells. Primary cell cultures from the ascitic fluid of three patients at diagnosis, two patients chemo-resistant to carboplatin and paclitaxel, and one patient treated with letrozole for breast cancer were studied and compared to the ovarian cancer cell lines A2780 and PTX10, by cell viability assay (MTS). Effects on cell cycle modulation and apoptosis were examined by flow cytometry and Western blot analysis (WB). WB was further conducted to investigate protein expressions altered by PACs. The results show that IC(50) of the primary cultures ranged from 0.6 to 5.4 μg/ml for oridonin and 0.3-12.7 μg/ml for wogonin. The paclitaxel-resistant cell line PTX10 was more sensitive to each of the PACs than the chemo-sensitive cell line A2780. Of particular interest is that in combination, the two PACs were synergistic in their cytotoxicity to five of six of the primary cultures and to both the cell lines (combination indices of 0.39-0.95). The inhibition is attributable to apoptosis and cell cycle modulation induced by the PACs as demonstrated in A2780 and PTX10. Up-regulation of the functional p53 protein in A2780 and down-regulation of Akt protein in PTX10 have in part contributed to the apoptosis. These findings suggest that oridonin and wogonin may have activity in ovarian cancer following its development of resistance to carboplatin and paclitaxel.

Topics: Aged; Antigens, Neoplasm; Ascites; Biomarkers, Tumor; Cell Adhesion Molecules; Cell Cycle; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Shape; Cell Survival; Diterpenes, Kaurane; Drug Screening Assays, Antitumor; Drug Therapy, Combination; Epithelial Cell Adhesion Molecule; Epithelial Cells; Female; Flavanones; Humans; Inhibitory Concentration 50; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Neoplastic Stem Cells; Ovarian Neoplasms; Prostatic Neoplasms; Staining and Labeling

The androgen receptor (AR) signaling pathway continues to be active in hormone resistant prostate cancer (HRPC) and can inappropriately activate transcription. Consequently the AR is a therapeutic target for HRPC. We reported that PC-SPES is active against HRPC, partly due to its actions in down-regulating AR protein expression and modulating cell cycle. Further investigation has identified five active anticancer compounds. This study describes the effects of three of these compounds (oridonin, isoliquiritigenin and wogonin) on cell proliferation, cell apoptosis, cell cycle parameters, AR and PSA protein expression. In each case, these compounds have independent activities which may partly contribute to the biological activity of PC-SPES.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Chalcones; Diterpenes; Diterpenes, Kaurane; Flavanones; Gene Expression Regulation, Neoplastic; Humans; Male; Plant Extracts; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen