Selective anti-cancer effects of plasma-activated medium and its high efficacy with cisplatin on hepatocellular carcinoma with cancer stem cell characteristics

Yan Li, Tianyu Tang, Hae June Lee, Kiwon Song

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12 Citations (Scopus)


Hepatocellular carcinoma (HCC) is a major histological subtype of primary liver cancer. Ample evidence suggests that the pathological properties of HCC originate from hepatic cancer stem cells (CSCs), which are responsible for carcinogenesis, recurrence, and drug resistance. Cold atmospheric-pressure plasma (CAP) and plasma-activated medium (PAM) induce apoptosis in cancer cells and represent novel and powerful anti-cancer agents. This study aimed to determine the anti-cancer effect of CAP and PAM in HCC cell lines with CSC characteristics. We showed that the air-based CAP and PAM selectively induced cell death in Hep3B and Huh7 cells with CSC characteristics, but not in the normal liver cell line, MIHA. We observed both caspase-dependent and-independent cell death in the PAM-treated HCC cell lines. Moreover, we determined whether combinatorial PAM therapy with various anti-cancer agents have an additive effect on cell death in Huh7. We found that PAM highly increased the efficacy of the chemotherapeutic agent, cisplatin, while enhanced the anti-cancer effect of doxorubicin and the targeted-therapy drugs, trametinib and sorafenib to a lesser extent. These findings support the application of CAP and PAM as anti-cancer agents to induce selective cell death in cancers containing CSCs, suggesting that the combinatorial use of PAM and some specific anti-cancer agents is complemented mechanistically.

Original languageEnglish
Article number3956
JournalInternational journal of molecular sciences
Issue number8
Publication statusPublished - 2021 Apr 2

Bibliographical note

Funding Information:
Funding: This research was supported by a grant from the National Research Foundation (NRF, No. NRF2020R1A2C1102153) and partly by the Bio & Medical Technology Development Program of NRF (No. NRF2016M3A9C6918275) funded by the Korean government (MSIT). Y.L. was partly supported by the post-BK program of the National Research Foundation of Korea (NRF).

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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