Paris saponin VII from trillium tschonoskii reverses multidrug resistance of adriamycin-resistant MCF-7/ADR cells via P-glycoprotein inhibition and apoptosis augmentation.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Saponins of several herbs are known to induce apoptosis in some cancer cells and are proposed to be promising modulators of drug resistance. In the present study, we extracted Paris saponin VII (PS VII), a kind of saponin, from Trillium tschonoskii Maxim. and observed its effect on adriamycin-resistant breast cancer cells.

MATERIALS AND METHODS:

An adriamycin-resistant human breast cancer cell line, MCF-7/ADR cells were exposed to different concentrations of PS VII (0-100 μmol/L). Then, flow cytometric assays and a human apoptosis array were used to detect apoptotic cells and apoptosis related protein expression. P-glycoprotein levels and intracellular rhodamine 123 (RH-123) accumulations were measured to evaluate the expression and activity of P-glycoprotein.

RESULTS:

PS VII dose dependently suppressed cell viability as well as triggered apoptosis and modulated drug resistance of MCF-7/ADR cells. Further results showed that PS VII treatment in MCF-7/ADR cells led to increased TNFR1, TRAIL R1/DR4, TRAIL R2/DR5, and FADD expression, and activation of PARP, caspase-8, and 3. In parallel to the alterations, P-glycoprotein expression and activity were also reduced.

CONCLUSION:

These findings showed that PS VII might be an effective tumouristatic agent for the treatment of MDR breast cancer.

• Authors: Yuhua Li, Lei Fan, Yang Sun, Xia Miao, Feng Zhang, Jin Meng, Jing Han, Dian Zhang, Rong Zhang, Zhenggang Yue, Qibing Mei
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 154 Issue 3 Pg. 728-34 (Jul 03 2014) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 24818584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• Paris saponin VII
• Saponins
• Doxorubicin

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (antagonists & inhibitors, metabolism)
• Antineoplastic Agents, Phytogenic (chemistry, isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Doxorubicin (pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drug Screening Assays, Antitumor
• Humans
• MCF-7 Cells
• Saponins (chemistry, isolation & purification, pharmacology)
• Structure-Activity Relationship
• Trillium (chemistry)
• Tumor Cells, Cultured