Transportation of berberine into HepG2, HeLa and SY5Y cells: a correlation to its anti-cancer effect.
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.
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Yu-Nong
YN
Pang
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Yin-Wen
YW
Liang
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Tian-Shi
TS
Feng
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Shuang
S
Zhao
NGM Biopharmaceuticals, Inc., South San Francisco, California, United States of America.
Hao
H
Wu
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Yu-Shuang
YS
Chai
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Fan
F
Lei
Drug Discovery Facility, School of Life Sciences, Tsinghua University, Beijing, China.
Yi
Y
Ding
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Dong-Ming
DM
Xing
MOE Key Laboratory of Protein Sciences, Laboratory of Molecular Pharmacology and Pharmaceutical Sciences, School of Life Sciences and School of Medicine, Tsinghua University, Beijing, China.
Li-Jun
LJ
Du
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001599:Berberine / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001692:Biological Transport; D045744:Cell Line, Tumor; D015870:Gene Expression; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D001599:Berberine