PMID- 34848465
OWN - NLM
STAT- MEDLINE
DCOM- 20211215
LR  - 20211215
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 41
IP  - 12
DP  - 2021 Dec
TI  - Differences in Transport Characteristics and Cytotoxicity of Epirubicin and 
      Doxorubicin in HepG2 and A549 Cells.
PG  - 6105-6112
LID - 10.21873/anticanres.15430 [doi]
AB  - BACKGROUND/AIM: Epirubicin (EPI), an epimer of doxorubicin (DOX), and DOX are 
      anthracycline agents with broad-spectrum antitumor activity. The aim of the 
      present study was to elucidate the transport characteristics of EPI and DOX in 
      human hepatocellular carcinoma HepG2 cells and human non-small cell lung cancer 
      A549 cells, and to examine the relationship of intracellular drug accumulation 
      with their cytotoxic effects. MATERIALS AND METHODS: Intracellular concentrations 
      of EPI and DOX were measured using high-performance liquid chromatography (HPLC). 
      Expression level of targeted genes was analyzed by real-time quantitative PCR. 
      Cell viability was evaluated using the MTT assay. RESULTS: Similar to DOX, EPI 
      was taken up into HepG2 and A549 cells by organic cation transporter 6 and 
      passive diffusion; however, the efficiency of saturable and non-saturable uptake 
      of EPI was greater than that of DOX in both cell types. EPI served as a substrate 
      of P-glycoprotein and multidrug associated protein (MRP) 1 and MRP2 similarly to 
      DOX, but the efflux efficiency of each transporter was markedly different between 
      EPI and DOX. The intracellular accumulation of EPI was significantly greater than 
      that of DOX in all cells, and the accumulated level reflected the cytotoxic 
      effects of these drugs. However, the intracellular drug amount did not correspond 
      to the degree of cytotoxicity when compared between HepG2 and A549 cells, which 
      can be explained by the higher expression of Bcl-xl in A549 cells. CONCLUSION: 
      This study suggested that the transport characteristics are markedly different 
      between EPI and DOX in HepG2 and A549 cells, and that intracellular accumulation 
      is the predominant factor affecting the cytotoxicity of EPI and DOX in individual 
      cells.
CI  - Copyright (c) 2021 International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Nagai, Katsuhito
AU  - Nagai K
AD  - Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka 
      Ohtani University, Tondabayashi, Japan nagaika@osaka-ohtani.ac.jp.
FAU - Fukuno, Shuhei
AU  - Fukuno S
AD  - Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka 
      Ohtani University, Tondabayashi, Japan.
FAU - Shiota, Maho
AU  - Shiota M
AD  - Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka 
      Ohtani University, Tondabayashi, Japan.
FAU - Tamura, Mayuko
AU  - Tamura M
AD  - Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka 
      Ohtani University, Tondabayashi, Japan.
FAU - Yabumoto, Sayaka
AU  - Yabumoto S
AD  - Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka 
      Ohtani University, Tondabayashi, Japan.
FAU - Konishi, Hiroki
AU  - Konishi H
AD  - Laboratory of Clinical Pharmacy and Therapeutics, Faculty of Pharmacy, Osaka 
      Ohtani University, Tondabayashi, Japan.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 3Z8479ZZ5X (Epirubicin)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - A549 Cells/*drug effects
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Doxorubicin/*pharmacology
MH  - Epirubicin/*pharmacology
MH  - Hep G2 Cells/*drug effects
MH  - Humans
OTO - NOTNLM
OT  - A549 cell
OT  - Epirubicin
OT  - HepG2 cell
OT  - cytotoxicity
OT  - doxorubicin
OT  - transport
EDAT- 2021/12/02 06:00
MHDA- 2021/12/16 06:00
CRDT- 2021/12/01 06:05
PHST- 2021/08/07 00:00 [received]
PHST- 2021/10/15 00:00 [revised]
PHST- 2021/10/18 00:00 [accepted]
PHST- 2021/12/01 06:05 [entrez]
PHST- 2021/12/02 06:00 [pubmed]
PHST- 2021/12/16 06:00 [medline]
AID - 41/12/6105 [pii]
AID - 10.21873/anticanres.15430 [doi]
PST - ppublish
SO  - Anticancer Res. 2021 Dec;41(12):6105-6112. doi: 10.21873/anticanres.15430.