Guajadial reverses multidrug resistance by inhibiting ABC transporter expression and suppressing the PI3K/Akt pathway in drug-resistant breast cancer cells.

Abstract

Multidrug resistance remains a major challenge in the chemotherapy of breast cancer. Guajadial, a natural meroterpenoid, has been found to possess anti-tumor activity. However, the role of guajadial in drug resistance has not been investigated. The aim of this study was to evaluate the effect of guajadial on drug resistance in drug-resistant breast cancer cells. Cell viability was measured by MTT assay, and the IC50 values were calculated. The expression of ATP-binding cassette (ABC) transporters including P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP) was detected by qRT-PCR and western blot. The expression of Akt, p-Akt, p70S6K, and p-p70S6K was determined by western blot. We found that guajadial significantly inhibited cell viability of parental non-resistant cell line MCF-7, adriamycin (ADR)-resistant cell line MCF-7/ADR, and paclitaxel (PTX)-resistant cell line MCF-7/PTX in a dose-dependent manner. Guajadial enhanced ADR and PTX sensitivity of MCF-7/ADR and MCF-7/PTX cells, and inhibited the expression of P-gp and BCRP. Guajadial treatment resulted in an inactivation of PI3K/Akt pathway in drug-resistant MCF-7 cells. In conclusion, guajadial acted as an inhibitor of drug resistance, which might be mediated by the inhibition of ABC transporter expression and PI3K/Akt pathway in drug-resistant breast cancer cells. These findings suggested that guajadial treatment might be a new approach to overcome the drug resistance in the chemotherapy of breast cancer.

• Authors: Yaxun Li, Zhenhua Zhai, Hao Li, Xudong Wang, Yinpeng Huang, Xin Su
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 305 Pg. 98-104 (May 25 2019) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 30929998 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier B.V.

Chemical References

• ATP-Binding Cassette Transporters
• Terpenes
• guajadial
• Doxorubicin
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Ribosomal Protein S6 Kinases, 70-kDa
• Paclitaxel

Topics

• ATP-Binding Cassette Transporters (antagonists & inhibitors, genetics, metabolism)
• Breast Neoplasms (metabolism, pathology)
• Cell Survival (drug effects)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• MCF-7 Cells
• Paclitaxel (pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Ribosomal Protein S6 Kinases, 70-kDa (genetics, metabolism)
• Signal Transduction (drug effects)
• Terpenes (pharmacology)