Baicalein decreases side population proportion via inhibition of ABCG2 in multiple myeloma cell line RPMI 8226 in vitro.
OBJECTIVE
To investigate the effect of baicalein on side population in human multiple myeloma cell line RPMI 8226 and the underlying molecular mechanisms in vitro and in silico.


METHODS
MTT assay was applied to detect the anti-proliferation effect of baicalein. The detection of side population cells is based on the Hoechst 33342 exclusion assay technique and flow cytometric analysis. Western blotting assay was used to explore the expression of ABCG2 protein. Homology modeling and molecular docking were performed with Discovery Studio 2.1.


RESULTS
Baicalein decreased both cell viability with IC50=168.5 μM and the proportion of SP cells in a dose-dependent manner. Correspondingly, it significantly decreased the expression level of ABCG2 protein. Baicalein also shared similar binding sites and modes with fumitremorgin C to the protein.


CONCLUSIONS
Baicalein possessed novel anticancer properties, such as anti-proliferation and drug efflux inhibition in side population cells, which suggested its potential feature of targeting cancer stem cells of multiple myeloma.
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Yue-Yu
YY
Gu
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Li-Ping
LP
Liu
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Jian
J
Qin
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Meng
M
Zhang
Faculty of Pharmacy, The University of Sydney, NSW 2006, Australia; Kiang Wu Hospital, Macau, China.
Yuling
Y
Chen
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
Dongmei
D
Wang
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
Zhi
Z
Li
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: babytangzai@21cn.com.
Jing-Zhong
JZ
Tang
The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: mosuilin@mail.sysu.edu.cn.
Sui-Lin
SL
Mo
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D058985:Side-Population Cells / Q000187:drug effects
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D044950:Flavanones; D009363:Neoplasm Proteins; C006680:baicalein
ABCG2; Baicalein; Baicalein (PubChem CID: 5281605); Fumitremorgin C (FTC) (PubChem CID: 403923); Methyl sulfoxide (DMSO) (PubChem CID: 679); Multiple myeloma; Propidium iodide (PI) (PubChem CID: 104981); Side population