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

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.

• Authors: Entidhar Al Sawah, 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
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 141 Issue 2 Pg. 237-42 (Feb 2015) ISSN: 1432-1335 [Electronic] Germany
• PMID: 25164128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• RNA, Messenger
• Saponins
• polyphyllin D
• Diosgenin
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Biomarkers, Tumor (genetics)
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Diosgenin (analogs & derivatives, pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Gene Expression Profiling
• Humans
• Oligonucleotide Array Sequence Analysis
• Ovarian Neoplasms (drug therapy, genetics, pathology)
• RNA, Messenger (genetics)
• Real-Time Polymerase Chain Reaction
• Reverse Transcriptase Polymerase Chain Reaction
• Saponins
• Signal Transduction (drug effects)
• Tumor Cells, Cultured