TY - JOUR
T1 - Alpha-mangostin Reduces Cell Viability in Sorafenib-surviving Cells by Modulating Multiple Drug Transporters in Hepg2 Hepatocellular Carcinoma Cells
AU - Wangsaputra, Vincent Kharisma
AU - Syarinta, Syarinta
AU - Louisa, Melva
N1 - Funding Information:
The authors acknowledge the Indonesian Ministry of Research and Technology, National Research and Innovation Agency, for providing the Basic Research and Higher Education Excellence Grant 2020.
Publisher Copyright:
© 2021 Vincent Kharisma Wangsaputra et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
PY - 2021/6
Y1 - 2021/6
N2 - A previous study showed that alpha-mangostin (AM) showed benefit when given to sorafenib (SOR)-surviving cells. However, the mechanism was not fully understood. The present study aimed to understand the effect of AM on SOR-surviving cells and its agent concerning drug transporters. SOR-surviving cells were treated with SOR 10 μM. Surviving cells were divided into four groups of treatment, namely, vehicle only dimethyl sulfoxide (DMSO), SOR 10 μM, AM 20 μM, or combination of SOR 10 μM-AM 20 μM. As controls, HepG2 naïve cells were treated with DMSO only or AM 20 μM. Cell viability was counted using trypan blue exclusion assay. Simultaneously, the mRNA expressions of P-glycoprotein (P-gp), ABCG2, MRP2, MRP3, OCT1, and OATP1B3 drug transporters were examined with quantitative reverse transcriptase-polymerase chain reaction. Decreased mRNA expression of P-gp was found in SOR-surviving cells treated with SOR. In contrast, AM alone or SOR's combination caused a significant increase in both efflux and influx transporters, no difference in fold increase of all transporters evaluated in AM versus SOR-AM combinations. Generally, AM treatment increased the mRNA expression of all the drug transporters.
AB - A previous study showed that alpha-mangostin (AM) showed benefit when given to sorafenib (SOR)-surviving cells. However, the mechanism was not fully understood. The present study aimed to understand the effect of AM on SOR-surviving cells and its agent concerning drug transporters. SOR-surviving cells were treated with SOR 10 μM. Surviving cells were divided into four groups of treatment, namely, vehicle only dimethyl sulfoxide (DMSO), SOR 10 μM, AM 20 μM, or combination of SOR 10 μM-AM 20 μM. As controls, HepG2 naïve cells were treated with DMSO only or AM 20 μM. Cell viability was counted using trypan blue exclusion assay. Simultaneously, the mRNA expressions of P-glycoprotein (P-gp), ABCG2, MRP2, MRP3, OCT1, and OATP1B3 drug transporters were examined with quantitative reverse transcriptase-polymerase chain reaction. Decreased mRNA expression of P-gp was found in SOR-surviving cells treated with SOR. In contrast, AM alone or SOR's combination caused a significant increase in both efflux and influx transporters, no difference in fold increase of all transporters evaluated in AM versus SOR-AM combinations. Generally, AM treatment increased the mRNA expression of all the drug transporters.
KW - Alpha-mangostin
KW - drug transporters
KW - OCT1
KW - P-glycoprotein
KW - sorafenib resistance
UR - http://www.scopus.com/inward/record.url?scp=85108813859&partnerID=8YFLogxK
U2 - 10.7324/JAPS.2021.110612
DO - 10.7324/JAPS.2021.110612
M3 - Article
AN - SCOPUS:85108813859
SN - 2231-3354
VL - 11
SP - 105
EP - 110
JO - Journal of Applied Pharmaceutical Science
JF - Journal of Applied Pharmaceutical Science
IS - 6
ER -
