PMID- 32319656
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20211022
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Linking)
VI  - 44
IP  - 1
DP  - 2020 Jul
TI  - Icariside II overcomes BRAF inhibitor resistance in melanoma by inducing ROS 
      production and inhibiting MITF.
PG  - 360-370
LID - 10.3892/or.2020.7582 [doi]
AB  - Metastatic melanoma is the most aggressive skin cancer. Although BRAF inhibitor 
      treatment has achieved great success in melanoma, resistance develops within 
      12 months. Icariside II (IS), a natural compound extracted from Herba Epimedii, 
      exerts anticancer properties. In the present study, we determined by MTT, flow 
      cytometry and western blotting, respectively that IS potentiated the 
      PLX4032‑induced downregulation of cell viability and increase in apoptosis and 
      autophagy in BRAF inhibitor‑resistant melanoma. In addition, we also revealed by 
      flow cytometry and western blotting, respectively, that IS combined with PLX4032 
      increased mitochondrial and intracellular reactive oxygen species (ROS) 
      generation and subsequently promoted depolarization of mitochondria and release 
      of apoptotic proteins. N‑acetyl cysteine (NAC) and glutathione (GSH), ROS 
      scavengers, reversed the IS‑induced enhancement of the response to PLX4032. 
      Microphthalmia‑associated transcription factor (MITF) and tyrosine‑protein kinase 
      Met (c‑Met) are well‑known factors that contribute to BRAF inhibitor resistance. 
      Furthermore, c‑Met is a direct transcriptional target of MITF in melanocytes and 
      melanoma cells. It was also revealed that IS markedly inhibited MITF and c‑Met 
      expression partially by increasing ROS production in BRAF inhibitor‑resistant 
      melanoma cells.
FAU - Liu, Xiao
AU  - Liu X
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, 
      P.R. China.
FAU - Li, Zheng
AU  - Li Z
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, 
      P.R. China.
FAU - Li, Ming
AU  - Li M
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, 
      P.R. China.
FAU - Chai, Jingxiu
AU  - Chai J
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, 
      P.R. China.
FAU - He, Shan
AU  - He S
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, 
      P.R. China.
FAU - Wu, Jinfeng
AU  - Wu J
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, 
      P.R. China.
FAU - Xu, Jinhua
AU  - Xu J
AD  - Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, 
      P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20200415
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Flavonoids)
RN  - 0 (MITF protein, human)
RN  - 0 (Microphthalmia-Associated Transcription Factor)
RN  - 0 (Reactive Oxygen Species)
RN  - 113558-15-9 (baohuoside I)
RN  - 207SMY3FQT (Vemurafenib)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.1 (BRAF protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins B-raf)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Down-Regulation
MH  - Drug Resistance, Neoplasm/drug effects
MH  - Drug Synergism
MH  - Flavonoids/*pharmacology
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - Melanoma/drug therapy/*genetics/metabolism
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Microphthalmia-Associated Transcription Factor/*genetics
MH  - Proto-Oncogene Proteins B-raf/*genetics
MH  - Proto-Oncogene Proteins c-met/genetics
MH  - Reactive Oxygen Species/*metabolism
MH  - Vemurafenib/*pharmacology
OTO - NOTNLM
OT  - icariside II
OT  - melanoma
OT  - BRAF inhibitor resistance
OT  - reactive oxygen species
OT  - MITF
EDAT- 2020/04/23 06:00
MHDA- 2021/03/09 06:00
CRDT- 2020/04/23 06:00
PHST- 2019/09/24 00:00 [received]
PHST- 2020/03/18 00:00 [accepted]
PHST- 2020/04/23 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/04/23 06:00 [entrez]
AID - 10.3892/or.2020.7582 [doi]
PST - ppublish
SO  - Oncol Rep. 2020 Jul;44(1):360-370. doi: 10.3892/or.2020.7582. Epub 2020 Apr 15.