Table I.
Antitumor activity of ART in different cancer types.
| First author/s, year | Cancer type | Model/cell line | Mechanism/results | (Refs.) |
|---|---|---|---|---|
| Ishikawa et al, 2020 | ATLL | HTLV-1 | Cyclin-dependent kinase 1, 2, 4 and 6 ↑, cyclin B1, D2 and E ↓; p21 ↑; intracellular reactive oxygen species ↑; JunB↓; JunD↓ | (5) |
| Chen et al, 2020 | Leukemia | HL-60 and KG1a cells | Induced cell apoptosis and inhibited cell proliferation and stemness in a dose-dependent manner via the suppression of the MEK/ERK and PI3K/Akt pathways | (34) |
| Hu et al, 2019 | Leukemia | MV4-11 | Caspase-3 ↑; autophagy-related protein LC3B ↑; Bcl-2 ↓ | (58) |
| Kim et al, 2015 | CML | KBM-5 | Antiproliferative and proapoptotic effects through suppression of multiple signaling cascades | (59) |
| Kumar et al, 2017 | AML | AML MV4-11 and MOLM-13 | Cellular and mitochondrial ROS accumulation, double-stranded DNA damage, loss of mitochondrial membrane potential and induction of the intrinsic mitochondrial apoptotic cascade | (60) |
| Wang et al, 2017 | Pituitary adenoma | GH3 and MMQ | ART and BRC used in combination exert synergistic apoptotic and antitumor effects by suppressing miR-200c and stimulating PTEN expression | (61) |
| Karpel-Massler et al, 2014 | Glioblastoma | U87MG and A172 | A combination of ART and temozolomide resulted in increased cytotoxicity | (62) |
| Berte et al, 2016 | Glioblastoma | LN229 and A172 | Downregulation of RAD51 protein expression and HR activity. Inhibition of senescence induced by TMZ | (63) |
| Lian et al, 2016 | Glioma | SHG44 | Inhibition of cell proliferation, migration and invasion, and increase of cell apoptosis | (64) |
| Berdelle et al, 2011 | Glioblastoma | LN-229 | Oxidative DNA damage and DNA double-strand breaks, leading to tumor cell death | (65) |
| Button et al, 2014 | Schwannoma | RT4 | Combination with the autophagy inhibitor chloroquine potentiated cell death | (66) |
| Wei et al, 2020 | Glioma | U251, U87, U138 and SK-N-SH | Impairing the nuclear localization of protein SREBP2 and the expression of target genes HMGCR through the mevalonate pathway, further affecting the metabolism of glioma cells | (67) |
| Greenshields et al, 2019 | Breast cancer | MDA-MB-468 and SK-BR-3 cells | Inhibition of breast cancer cell proliferation via a ROS-dependent G2/M arrest and ROS-independent G1 arrest | (68) |
| Wen et al, 2018 | Breast cancer | MCF7 cells | Inhibition of cell proliferation and increased G2/M arrest through ATM activation and the ‘ATM-Chk2-CDC25C’ pathway | (69) |
| Greenshields et al, 2017 | Ovarian cancer | Ovarian cancer cells | Induction of ROS; reduced proliferation; altered expression of cell cycle regulatory proteins, including cyclin D3, E2F-1 and p21; inhibition of mTOR signaling | (70) |
| Chen et al, 2019 | Ovarian cancer | ID8 | miR-142 expression in peripheral CD4+ T cells ↑; Sirt1 levels ↓; Th1 differentiation from CD4+ T cells ↑ | (35) |
| Li et al, 2018 | Ovarian cancer | SKOV3 and primary EOC | Induction of autophagy; cell cycle arrest; inhibition of EOC growth | (71) |
| Liu et al, 2015 | Esophageal cancer | Eca109 and Ec9706 | By downregulating mitochondrial membrane potential, Bcl-2 and CDC25A, upregulating Bax and caspase-3, induction of cell apoptosis and cell cycle arrest; concentration-dependent inhibitory activity in vivo and in vitro | (72) |
| Fei et al, 2018 | Esophageal cancer | Irradiated TE-1 cells in vitro and in vivo | p21 ↑; cyclin D1, RAD51, RAD54, Ku70 and Ku86 protein ↓ | (42) |
| Wang et al, 2018 | Esophageal cancer | Eca109/ABCG2, xenograft tumor mouse model | Suppression of esophageal cancer drug resistance through the regulation of ABCG2 expression | (73) |
| Wang et al, 2017 | Gastric cancer | SGC-7901 | Inhibition of the cell growth; induction of apoptosis; may be related to the regulation of CDC25A, Bcl-2, Bax, caspase-3 and mitochondrial membrane potential | (74) |
| Zhang et al, 2015 | Gastric cancer | HGC-27 cells | COX-2 ↓; Bax↑; Bcl-2 ↓; caspase-3 ↓; caspase-9 ↓ | (75) |
| Jiang et al, 2018 | Colon cancer | HCT116; in vitro and in vivo | Mitochondrial cleaved caspase 3, PARP, caspase-9 and Bcl-2-associated X protein ↑; Bcl-2 ↓ | (76) |
| Kumar et al, 2019 | Colorectal cancer | Rat model | Inhibition of cellular influx; decreased the levels of oxidative stress and inflammatory markers; cyclooxygenase-2, inducible nitric oxide synthase, NF-κB, and IL-1β ↓ | (77) |
| Verma et al, 2017 | Colon carcinogenesis | Rat model | β-catenin signaling ↓; angiogenic markers (VEGF, MMP-9) ↓; inhibition of cell proliferation | (27) |
| Li et al, 2019 | Liver cancer | HepG2 and Huh7 | Increased the expression levels of cleaved caspase-9 and cleaved poly ADP ribose polymerase, reduced VEGFR2 protein expression and reduced cell migration | (22) |
| Ilamathi et al, 2016 | Hepatocellular carcinoma | HepG2 | Suppression of STAT3; increased apoptosis | (78) |
| Wang et al, 2020 | Lung cancer | A549 | Reduced cell clone numbers; cell cycle arrest at the G2/M phase; cell cycle and apoptosis-related proteins BAX, p21, p53 and caspase-3 ↑; Bcl-2 and cyclin B1 expression ↓ | (24) |
| Zhao et al, 2020 | Lung cancer | A549 | Induction cell apoptosis and cell cycle arrest, Bcl-2 protein ↓; mitochondrial membrane potential ↓; Bax protein ↑ | (25) |
ART, artesunate; ATLL, adult T-cell leukemia/lymphoma; AML, acute myeloid leukemia; CML, chronic myeloid leukemia; ROS, reactive oxygen species; HMGCR, 3-hydroxy-3-methylglutaryl-CoA reductase; SREBP2, sterol regulatory element-binding protein 2; Chk2, checkpoint kinase 2; CDC25, cell division cycle 25C; miR, microRNA; Sirt1, sirtuin 1; ABCG2, ATP binding cassette subfamily G member 2; COX-2, cyclo-oxygenase-2; PARP, poly(ADP-ribose) polymerase; BRC, bromocriptine; TMZ, temozolomide.