Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells

Abstract

The resistance of cancer to chemotherapeutic agents is a major obstacle during chemotherapy. Clinical multidrug resistance (MDR) is commonly mediated by membrane drug efflux pumps, including ATP‑binding cassette subfamily B member 1, also termed P-glycoprotein (P-gp). P-gp is a membrane transporter encoded by the MDR1 gene. The current study aimed to investigate the impact of psoralen on the expression and function of P‑gp. The 10% inhibitory concentration (IC10) of psoralen, and its capacity to reduce MDR in adriamycin (ADR)‑resistant MCF‑7/ADR cells were determined using MTT assay. The ability of psoralen to modulate the transport activity of P‑gp in MCF‑7/ADR cells was evaluated by measuring the accumulation and efflux of rhodamine 123 (Rh 123) and adriamycin with flow cytometry. The present study evaluated the mRNA level of MDR1 in MCF‑7 and MCF‑7/ADR cells treated with psoralen using reverse transcription-quantitative polymerase chain reaction. The protein expression level of P‑gp was examined by western blot analysis. The current study demonstrated that the IC10 of psoralen in MCF‑7/ADR cells was 8 µg/ml. At 8 µg/ml, psoralen reduced MDR and the sensitivity of the MCF‑7/ADR cells to ADR compared with untreated cells. Additionally, psoralen significantly increased the intracellular accumulation of ADR and Rh 123. However, the IC10 of psoralen did not affect the protein expression levels of P‑gp or mRNA levels of MDR1 (P>0.05). Psoralen reduces MDR by inhibiting the efflux function of P‑gp, which may be important for increasing the efficiency of chemotherapy and improving the clinical protocols aiming to reverse P-gp-mediated MDR.

Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

“…P-gp transports hydrophobic substrates, lipids, steroids, antibiotics, antihistamines, anticancer drugs such as anthracyclines, vinka alkaloids, and taxanes [25]. Its upregulation has been identified in many types of cancer and it has been conclusively linked to poor clinical outcomes in breast cancer, ovarian cancer, gastric cancer, and acute myelogenous leukemia [26,27,28,29]. In NSCLC, emerging evidence has proven that the response to chemotherapy in NSCLC patients is related to MDR1 expression.…”

<p>Psoralen-loaded lipid-polymer hybrid nanoparticles enhance doxorubicin efficacy in multidrug-resistant HepG2 cells</p>

“…However, Jiang et al 38 demonstrated that the intracellular drug accumulation was significantly increased in MCF7/ADR cells after treatment with PSO, whereas the P-gp expression at the mRNA or protein level was unaffected. 37,38 Hsieh et al 11 revealed that PSO suppressed P-gp activity and decreased mRNA and proteins levels of P-gp in A549/D16 cell. However, the effects of P-gp on the extent of drug accumulation are highly dependent on its level of expression and the respective concentration of drug.…”

Fabrication of psoralen-loaded lipid-polymer hybrid nanoparticles and their reversal effect on drug resistance of cancer cells

“…Psoralen (PSO), a natural coumarin compound, which is popular in traditional Chinese medicine, has antitumor, estrogen-like and multi-drug resistance modulating properties (14)(15)(16). However, its use has been limited due to poor solubility.…”