Cold Atmospheric Plasma and Silymarin Nanoemulsion Activate Autophagy in Human Melanoma Cells

被引：47
作者：
Adhikari, Manish [1 ]
Adhikari, Bhawana [1 ]
Ghimire, Bhagirath [1 ]
Baboota, Sanjula [2 ]
Choi, Eun Ha [1 ]
机构：
[1] Kwangwoon Univ, Dept Elect & Biol Phys, Appl Plasma Med Ctr, Plasma Biosci Res Ctr, Seoul 01897, South Korea
[2] Jamia Hamdard, Sch Pharmaceut Educ & Res, Dept Pharmaceut, Delhi 110062, India
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 06期
基金：
新加坡国家研究基金会;
关键词：
cold atmospheric plasma; autophagy; silymarin nanoemulsion; PI3K; mTOR pathway; GOLD NANOPARTICLES; GLUCOSE-UPTAKE; CANCER; MECHANISMS; RESISTANCE; APOPTOSIS; PATHWAYS; THERAPY; STRESS; TUMORS;
D O I：
10.3390/ijms21061939
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Background: Autophagy is reported as a survival or death-promoting pathway that is highly debatable in different kinds of cancer. Here, we examined the co-effect of cold atmospheric plasma (CAP) and silymarin nanoemulsion (SN) treatment on G-361 human melanoma cells via autophagy induction. Methods: The temperature and pH of the media, along with the cell number, were evaluated. The intracellular glucose level and PI3K/mTOR and EGFR downstream pathways were assessed. Autophagy-related genes, related transcriptional factors, and autophagy induction were estimated using confocal microscopy, flow cytometry, and ELISA. Results: CAP treatment increased the temperature and pH of the media, while its combination with SN resulted in a decrease in intracellular ATP with the downregulation of PI3K/AKT/mTOR survival and RAS/MEK transcriptional pathways. Co-treatment blocked downstream paths of survival pathways and reduced PI3K (2 times), mTOR (10 times), EGFR (5 times), HRAS (5 times), and MEK (10 times). CAP and SN co-treated treatment modulates transcriptional factor expressions (ZKSCAN3, TFEB, FOXO1, CRTC2, and CREBBP) and specific genes (BECN-1, AMBRA-1, MAP1LC3A, and SQSTM) related to autophagy induction. Conclusion: CAP and SN together activate autophagy in G-361 cells by activating PI3K/mTOR and EGFR pathways, expressing autophagy-related transcription factors and genes.
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页数：17
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