Background: Chemotherapy is the most common treatment for cancer. However, the ability of cancer cells simultaneously becoming resistant to different drugs, a phenomenon called multidrug resistance (MDR), remains a major difficulty to successful chemotherapy. The efflux transporter, P-glycoprotein (P-gp, encoded by ABCB1 gene), is reported to play an important role in MDR cancers. Although three generations of P-gp inhibitors have been developed, the outcomes of clinical trials did not provide promising results. The development of “fourth generation inhibitors” aims at identifying potent and relative non-toxic substances from natural products. 

Aim: The aim of the present study is to investigate the effect of β-carotene on human P-gp, and evaluate whether β-carotene has the potential to reverse MDR cancers.

Methods: HEK293 cell line harbored human ABCB1 gene was established. MTT assay was performed to examine the cytotoxicity of β-carotene. Real-time RT-PCR was conducted to confirm the P-gp expression. The doxorubicin accumulation assay, rhodamine123 efflux assay and calcein-AM uptake assay were carried out to examine the function of P-gp in the established HEK293 cells, and were also used to evaluate the effect of β-carotene on P-gp function as well.

Results: The IC₅₀ of β-carotene were 195µM and 175µM for HEK293 and HEK293/ABCB1 cell line, respectively. The ABCB1 mRNA expression in HEK293/ABCB1 cell line was not influenced by treatment of 100µM β-carotene for 24 and 48 hours. Results from doxorubicin accumulation assay, rhodamine123 efflux assay and calcein-AM uptake assay demonstrated that pretreated 10, 25, 50, 100µM β-carotene for 0.5 and 24 hours significantly inhibited P-gp function (p<0.01).

Conclusions: The results revealed that β-carotene is a potential human P-gp inhibitor. Whether it can reverse MDR cancer warrants further investigations.