An unconventional cancer-promoting function of methamphetamine in hepatocellular carcinoma
© 2023 Si et al..
For the past decade, the prevalence and mortality of methamphetamine (METH) use have doubled, suggesting that METH use could be the next substance use crisis worldwide. Ingested METH is transformed into other products in the liver, a major metabolic organ. Studies have revealed that METH causes deleterious inflammatory response, oxidative stress, and extensive DNA damage. These pathological damages are driving factors of hepatocellular carcinoma (HCC). Nonetheless, the potential role of METH in HCC and the underlying mechanisms remain unknown. Herein, we found a higher HCC incidence in METH abusers. METH promoted cellular proliferation, migration, and invasion in two human-derived HCC cells. Consistently, METH uptake promoted HCC progression in a xenograft mouse model. Mechanistically, METH exposure induced ROS production, which activated the Ras/MEK/ERK signaling pathway. Clearance of ROS by NAC suppressed METH-induced activation of Ras/ERK1/2 pathways, leading to arrest of HCC xenograft formation in nude mice. To the best of our knowledge, this is the first study to substantiate that METH promotes HCC progression and inhibition of ROS may reverse this process.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Life science alliance - 6(2023), 3 vom: 25. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Si, Zizhen [VerfasserIn] |
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| Links: |
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| Themen: |
44RAL3456C |
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| Anmerkungen: |
Date Completed 24.01.2023 Date Revised 26.01.2024 published: Electronic-Print Citation Status MEDLINE |
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| doi: |
10.26508/lsa.202201660 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351805095 |
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| 520 | |a For the past decade, the prevalence and mortality of methamphetamine (METH) use have doubled, suggesting that METH use could be the next substance use crisis worldwide. Ingested METH is transformed into other products in the liver, a major metabolic organ. Studies have revealed that METH causes deleterious inflammatory response, oxidative stress, and extensive DNA damage. These pathological damages are driving factors of hepatocellular carcinoma (HCC). Nonetheless, the potential role of METH in HCC and the underlying mechanisms remain unknown. Herein, we found a higher HCC incidence in METH abusers. METH promoted cellular proliferation, migration, and invasion in two human-derived HCC cells. Consistently, METH uptake promoted HCC progression in a xenograft mouse model. Mechanistically, METH exposure induced ROS production, which activated the Ras/MEK/ERK signaling pathway. Clearance of ROS by NAC suppressed METH-induced activation of Ras/ERK1/2 pathways, leading to arrest of HCC xenograft formation in nude mice. To the best of our knowledge, this is the first study to substantiate that METH promotes HCC progression and inhibition of ROS may reverse this process | ||
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| 700 | 1 | |a Yu, Zhaoying |e verfasserin |4 aut | |
| 700 | 1 | |a Pang, Qian |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shuangshuang |e verfasserin |4 aut | |
| 700 | 1 | |a Qian, Liyin |e verfasserin |4 aut | |
| 700 | 1 | |a Ruan, Yuer |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Liu |e verfasserin |4 aut | |
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