Selective Anti-Cancer Effects of Plasma-Activated Medium and Its High Efficacy with Cisplatin on Hepatocellular Carcinoma with Cancer Stem Cell Characteristics

• Published in: International journal of molecular sciences Vol. 22; no. 8; p. 3956
• Main Authors: Li, Yan, Tang, Tianyu, Lee, Hae June, Song, Kiwon
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.04.2021; MDPI
• Subjects: Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; Apoptosis - drug effects; Atmospheric pressure; Cancer therapies; Carcinogenesis; Carcinogenesis - drug effects; Carcinogens; Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - pathology; Caspase; caspase-dependent and -independent cell death; Cell adhesion & migration; Cell death; Cell Line - drug effects; Cell Line, Tumor - drug effects; Cell Proliferation - drug effects; Chemotherapy; Cisplatin; Cisplatin - pharmacology; cold atmospheric-pressure plasma (CAP); Combinatorial analysis; combinatorial therapy; Culture Media - pharmacology; Culture Media - radiation effects; Cytotoxicity; Dehydrogenases; DNA damage; Doxorubicin; Doxorubicin - pharmacology; Drug resistance; Drugs; Electrodes; Gas flow; Gases; Hepatocellular carcinoma; hepatocellular carcinoma cell lines Hep3B and Huh7 with cancer stem cell populations; Hepatocytes; Humans; Kinases; Liver - drug effects; Liver - pathology; Liver cancer; Liver Neoplasms - drug therapy; Liver Neoplasms - pathology; Low temperature resistance; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - radiation effects; Plasma; Plasma Gases; plasma-activated medium (PAM); Reagents; Stem cells; combinatorial therapy; caspase-dependent and -independent cell death; cold atmospheric-pressure plasma (CAP); plasma-activated medium (PAM); hepatocellular carcinoma cell lines Hep3B and Huh7 with cancer stem cell populations
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22083956

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.