이수재
2019-10-18T02:41:20Z
2019-10-18T02:41:20Z
2019-05
CELL COMMUNICATION AND SIGNALING, v. 17, no. 52
1478-811X
https://biosignaling.biomedcentral.com/articles/10.1186/s12964-019-0360-4
https://repository.hanyang.ac.kr/handle/20.500.11754/111226
BackgroundRecent studies claimed the important role of cold atmospheric plasma (CAP) with nanotechnology in cancer treatments. In this study, silymarin nanoemulsion (SN) was used along with air CAP as therapeutic agent to counter human melanoma.MethodsIn this study, we examined the combined treatment of CAP and SN on G-361 human melanoma cells by evaluating cellular toxicity levels, reactive oxygen and nitrogen species (RONS) levels, DNA damage, melanoma-specific markers, apoptosis, caspases and poly ADP-ribose polymerase-1 (PARP-1) levels using flow cytometer. Dual-treatment effects on the epithelial-mesenchymal transition (EMT), Hepatocyte growth factor (HGF/c-MET) pathway, sphere formation and the reversal of EMT were also assessed using western blotting and microscopy respectively. SN and plasma-activated medium (PAM) were applied on tumor growth and body weight and melanoma-specific markers and the mesenchymal markers in the tumor xenograft nude mice model were checked.ResultsCo-treatment of SN and air CAP increased the cellular toxicity in a time-dependent manner and shows maximum toxicity at 200nM in 24h. Intracellular RONS showed significant generation of ROS (<3 times) and RNS (<2.5 times) in dual-treated samples compared to control. DNA damage studies were assessed by estimating the level of -H2AX (1.8 times), PD-1 (>2 times) and DNMT and showed damage in G-361 cells. Increase in Caspase 8,9,3/7 (>1.5 times), PARP level (2.5 times) and apoptotic genes level were also observed in dual treated group and hence blocking HGF/c-MET pathway. Decrease in EMT markers (E-cadherin, YKL-40, N-cadherin, SNAI1) were seen with simultaneously decline in melanoma cells (BRAF, NAMPT) and stem cells (CD133, ABCB5) markers. In vivo results showed significant reduction in SN with PAM with reduction in tumor weight and size.ConclusionsThe use of air CAP using -DBD and the SN can minimize the malignancy effects of melanoma cells by describing HGF/c-MET molecular mechanism of acting on G-361 human melanoma cells and in mice xenografts, possibly leading to suitable targets for innovative anti-melanoma approaches in the future.
This work was supported by a grant from the National Research Foundation of Korea (NRF), which is funded by the Korean Government, Ministry of Science, ICT and Future Planning (MSIP) NRF-2016K1A4A3914113; and 2017M3A9G8084539. This work is also supported by the grant of the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by Ministry of Science and ICT (MSIT) (50535-2019). This work is also funded by Kwangwoon University in 2019-20.
en
BMC
Non thermal plasma
Silymarin nanoemulsion
Melanoma
HGF
c-MET
Cancer Stemness
Epithelial-mesenchymal transition
Cold atmospheric plasma and silymarin nanoemulsion synergistically inhibits human melanoma tumorigenesis via targeting HGF/c-MET downstream pathway
Article
1
17
10.1186/s12964-019-0360-4
1-14
CELL COMMUNICATION AND SIGNALING
Adhikari, Manish
Kaushik, Neha
Ghimire, Bhagirath
Adhikari, Bhawana
Baboota, Sanjula
Al-Khedhairy, Abdulaziz A.
Wahab, Rizwan
Lee, Su-Jae
Kaushik, Nagendra Kumar
Choi, Eun Ha
2019036141
S
COLLEGE OF NATURAL SCIENCES[S]
DEPARTMENT OF LIFE SCIENCE
sj0420