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. 2015 Feb;141(2):237-42.
doi: 10.1007/s00432-014-1797-x. Epub 2014 Aug 28.

The Chinese herb polyphyllin D sensitizes ovarian cancer cells to cisplatin-induced growth arrest

Entidhar Al Sawah  1 , Douglas C Marchion, Yin Xiong, Ingrid J Ramirez, Forough Abbasi, Bernadette M Boac, Stephen H Bush, Nadim Bou Zgheib, E Clair McClung, Beman R Khulpateea, Amy Berry, Ardeshir Hakam, Robert M Wenham, Johnathan M Lancaster, Patricia L Judson
Affiliations

The Chinese herb polyphyllin D sensitizes ovarian cancer cells to cisplatin-induced growth arrest

Entidhar Al Sawah et al. J Cancer Res Clin Oncol. 2015 Feb.

Abstract

Purpose: We evaluated the effects of polyphyllin D (PD), a natural compound with anti-neoplastic activity and a major component of the Chinese herb Paris polyphylla, on ovarian cancer (OVCA) cell line proliferation and platinum sensitivity.

Methods: A panel of 20 OVCA cell lines was subjected to PD treatment, MTS proliferation assays, and determination of IC50. Pre-treatment, baseline genome-wide Affymetrix expression analysis was performed on each cell line, and Pearson's correlation was performed to identify genes associated with OVCA PD sensitivity. Twelve cell lines were treated with PD with and without cisplatin, and the effects of PD on cisplatin IC50 were quantified. Genes associated with OVCA PD sensitivity were evaluated for associations with survival in a publically available clinico-genomic dataset of 218 patients with OVCA.

Results: Our results showed that PD exhibited anti-proliferative effects against all OVCA cell lines tested, with IC50 values ranging from 0.2 to 1.4 μm. Furthermore, in all cell lines, PD treatment significantly decreased cisplatin IC50 (mean IC50 reduction of 2.1 µm; P < 0.02). Pearson's correlation test identified 25 probe sets, representing 18 unique genes to be associated with PD sensitivity (FDR = 0). We found that one of these genes was associated with overall survival in women with OVCA: CLDN4 (P = 0.014).

Conclusion: Our findings highlight the value of PD as a natural product with anti-cancer properties, which may also enhance the activity of existing therapeutic agents.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
The chemical structure of polyphyllin D (PD; Cheung et al. 2005)
Fig. 2
Fig. 2
Polyphyllin D inhibits ovarian cancer cell line proliferation. Line graphs depict the survivability of OVCA cells cultured in the presence of increasing concentrations of PD. Cell viability was determined using the CellTiter96® MTS assay kit. Experiments were performed a minimum of 3 times
Fig. 3
Fig. 3
Polyphyllin D potentiates growth arrest induced by cisplatin. The effects of PD on cisplatin-induced growth arrest at 72 h were evaluated in OVCA cell lines using the CellTiter96® MTS assays. In an effort to isolate the effect of PD on cisplatin sensitivity, cells were incubated in the presence of increasing concentrations of cisplatin in the presence and absence of a fixed dose of PD. All experiments were performed a minimum of 3 times
Fig. 4
Fig. 4
Genes correlated with PD response may influence overall survival from OVCA. Kaplan–Meier curves depicting associations between the expression of CLDN4 gene and overall survival from OVCA (n = 218). Log-rank test P values indicate significance
See this image and copyright information in PMC

References

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