Abstract
The anti-cancer activities of berberine (BBR) have been reported extensively in various cancer cell lines. However, the minimal inhibitory concentrations of BBR varied greatly among different cell lines and very few studies have been devoted to elucidate this aspect. In this study, we employed three cancer cell lines, HepG2, HeLa and SY5Y, to compare the transportation and distribution of BBR. HPLC results demonstrated that BBR was capable of penetrating all the cell lines whereas the cumulative concentrations were significantly different. HepG2 cells accumulated higher level of BBR for longer duration than the other two cell lines. Molecular docking studies revealed the BBR binding site on P-glycoprotein 1 (P-gp). In addition, we elucidated that BBR regulated P-gp at both mRNA and protein levels. BBR induced the transcription and translation of P-gp in HeLa and SY5Y cells, whereas BBR inhibited P-gp expression in HepG2 cells. Further study showed that BBR regulates P-gp expression depending on different mechanisms (or affected by different factors) in different cell lines. To summarize, our study has revealed several mechanistic aspects of BBR regulation on P-gp in different cancer cell lines and might shed some useful insights into the use of BBR in the anti-cancer drug development.
Highlights
Berberine (BBR), an isoquinoline alkaloid, can be isolated from medicinal plants such as Rhizoma coptidis, Scutellaria baicalensis and Phellodendron amurense
The anti-cancer effect of BBR has been reported on many cancer cell lines, including PC12 cells [3], melanoma cells [4], breast cancer cells [5], human colon cancer cells [6], 3T3-L1 adipocytes [7], non-small cell human lung cancer cells [8], prostate cancer cells [9], liver cancer cells [10], cervical cancer cells [11], etc
It is reported that the minimal inhibitory concentration of BBR varied significantly among different cancer cell lines, from 10 nM (3.73 ng/ml) in colon carcinoma cell to 400 mM (149.2 mg/ml) in MHCC97-L cells, through an unknown mechanism [12,13]
Summary
Berberine (BBR), an isoquinoline alkaloid, can be isolated from medicinal plants such as Rhizoma coptidis, Scutellaria baicalensis and Phellodendron amurense. It is reported that the minimal inhibitory concentration of BBR varied significantly among different cancer cell lines, from 10 nM (3.73 ng/ml) in colon carcinoma cell to 400 mM (149.2 mg/ml) in MHCC97-L cells, through an unknown mechanism [12,13]. The inhibition of P-gp was found to increase the intracellular concentration of BBR [15]. Recent studies reported that BBR regulates P-gp at different extends in different cell lines [16]. Regulation of P-gp at mRNA and protein levels by BBR has not been reported yet
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