NDLI: Combined activity of oridonin and wogonin in advanced-stage ovarian cancer cells : Sensitivity of ovarian cancer cells to phyto-active chemicals

Content Provider	Springer Nature Link
Author	Chen, Sophie Cooper, Matt Jones, Matt Madhuri, Thumuluru Kavitha Wade, Julie Bachelor, Ashleigh Butler Manuel, Simon
Copyright Year	2010
Abstract	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 IC50 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.
Starting Page	133
Ending Page	147
Page Count	15
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	27
Issue Number	2
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-09-26
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Apoptosis Cell cycle Anti-proliferative activity Oridonin Ovarian cancer Wogonin Cell Biology Pharmacology/Toxicology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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