Transportation of Berberine into HepG2, HeLa and SY5Y Cells: A Correlation to Its Anti-Cancer Effect

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.

Antiviral activity of berberine

“…Berberine exhibits unusual biochemical and pharmacological activities, including antidiabetic [1], hypolipidemic [2], antihypertensive [3], anti-inflammatory [4], antidiarrheal [5], hepatoprotective [6], antidepressant [7], anticancer [8], antibacterial [9], and antiviral [10] properties. BBR is capable of penetrating all cell lines, but the cumulative concentration is the highest in Hep G-2 cells [11]. It can cross the blood-brain barrier when it is administrated systematically, and it has a protective effect on the central nervous system [12].…”

Xanthomegnin detection does not discriminate between Trichophyton rubrum and T. mentagrophytes complexes

“…HPLC relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material (Gerber et al, 2004). HPLC has been used for the following purposes: (i) medical [e.g., the identification of hemoglobin variants (Çürük et al, 1993) and the detection of vitamin D levels in blood serum (Ford, 2013) or vanillylmandelic acid (Lionetto et al, 2008)], (ii) legal [e.g., identification of performance enhancement drugs in urine (Boccard et al, 2011)], (iii) research [e.g., separating the components of a complex biological sample (Kutlar et al, 1986)], and (iv) industrial [e.g., production of pharmaceutical products (Pang et al, 2014)]. …”

Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolic pathway in hepatoma cells

“…Berberine exhibits disconnection between its excellent pharmacodynamics and poor pharmacokinetic properties both in vitro and in vivo 34 35 . Moreover, the main methods currently used to detect berberine in plasma concentration and tissues disposition are high performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrum (LC-MS) 36 37 38 39 . To better understand berberine’s antiproliferation activity in hepatoma cells, we investigated the cellular uptake, distribution and localization of berberine utilizing its fluorescent molecular properties 40 41 , by both of flow cytometry and CLSM methods.…”