Table 2.
Pre-clinical development for OSCs-targeting agents
| Therapeutic | Function of molecules | Study type and model | Mechanism | References |
|---|---|---|---|---|
| BYL719 | A new specific PI3Kα inhibitor | Different murine preclinical models of osteosarcoma | Tumor development and tumor ectopic bone formation by decreasing Ki67+ cells and tumor vascularization | Gobin et al. [53] |
| LY294002 | An inhibitor of phosphoinositide 3-kinases (PI3Ks) | Human osteosarcoma CSCs, in vitro study | Prevent phosphorylation of PKB/Akt via inhibition of PI3K phosphorylation activity, leading to G0/G1 cell cycle arrest and apoptosis | Gong et al. [108] |
| BRM270 as a compound from 7 seven sian medicinal plants | NF-κB inhibitor | An in vivo tumor metastasis model of nude mice for osteosarcoma | A NF-κB inhibitor via acting as a suppressor of NF-κB signaling cascade in multidrug resistance -induced stem like cancer-initiating cells | Kwon et al. [194] |
| parthenolide | NF-κB inhibitor and oxidative stress inducer | LM7 osteosarcoma cells, in vitro treatments | Parthenolide and ionizing radiation leads cell death in osteosarcoma cells, resulting in reduction in the viability of both the osteosarcoma cells and CD133+ CSCs | Zuch et al. [110] |
| MC1742 and MC2625 | HDAC inhibitors | CSCs, in vitro study | Can elevate acetyl-H3 and acetyl-tubulin levels, inhibited CSC sphere growth via apoptosis induction in osteosarcoma and Ewing sarcoma | Di Pompo et al. [195] |
| Bufalin | – | In vitro study, and in vivo (nude mice model) | Inhibits the differentiation and proliferation of CSCs from C1OS via targeting miR-148 Downregulate proliferation marker Ki67, resulting in inhibition of sphere forming and proliferation in human OSCs derived from the MG63 cell line |
Chang et al. [182, 183] |
| Salinomycin | Antibacterial and coccidiostat agent | Both in vitro and in vivo study (nude mice model) | Suppress the sarcosphere formation, expressions of Oct4 and Sox2. Inhibit Wnt/β-catenin pathway via degradation of β-catenin and can act as inhibitor of OSCs | Tang et al. [86] |
| CESPa | Nanoparticle | Both in vitro and in vivo study (mic model) | Effective inhibitor of tumor growth with promising efficacy in osteosarcoma-bearing mice, effectively target CSCs of osteosarcoma and cancer cells | Chen et al. [196] |
| Ap-SAL-NPb | Nanoparticle | Both in vitro and in vivo study (mic model) | Ap-SAL-NP kill CD133+ osteosarcoma CSCs | Ni et al. [197] |
| EGFR-SNPs | Nanoparticle | In vitro drug assessment | EGFR-SNPs decrease the osteosarcoma sphere-forming and CD133+ osteosarcoma CSCs while comparing with salinomycin and SNPs. Effectively enhance delivery of salinomycin to osteosarcoma cells | Yu et al. [198] |
| 5-Azacytidine | DNA methyltransferase (DNMT) inhibitor | Osteosarcoma cell lines Saos-2 and MG63 | Induce an increase of stemness features of OS cells in context of CD133, Sox2, OCT4 and Nanog overexpression, as well as high sarcospheres-forming efficiency | Tirino et al. [199] |
aSali-entrapped lipid-polymer nanoparticles conjugated with EGFR and CD133 aptamers
bSalinomycin-loaded PEGylated poly nanoparticles conjugated with CD133 aptamer