Table 2.
Therapeutic agents with reported activity on OS-CSCs subpopulations or related properties.
| Therapeutic agent | Proposed mechanisms of action | Effect on CSC/CSC properties | Reference |
|---|---|---|---|
| Parthenolide | NF-κB inhibition/oxidative stress induction | Sensitizes to ionizing radiation reducing the viability of CD133+ CSCs | [31] |
| BRM270 | NF-κB/CDK6/IL6 downregulation | Induces programmed cell death | [32] |
| BYL719 | PI3K inhibition | Induces cell cycle arrest and inhibits migration | [33] |
| LY294002 | PI3K inhibition | Induces cell cycle arrest and apoptosis in OS-sarcospheres | [34] |
| SB431542 | TGF-β inhibition | Reduces self-renewal and differentiation and increases chemosensitivity of OS-sarcospheres | [35] |
| miR-382 expression | YB-1 inhibition | Decreases OS-CSCs, reduces metastatic potential, and inhibits tumor formation from CD133+ OS cells | [36] |
| miR-29b-1 expression | — | Reduces sarcosphere formation and induces chemosensitization of OS cells | [37] |
| miR-133a inhibition | — | Reduces cell invasion of CD133+ OS cells and suppresses metastasis in combination with chemotherapy | [38] |
| lncRNA HIF2PUT | HIF-2α | Reduces CD133+ cells and impairs sphere-forming in OS cells | [39] |
| Metformin | AMPK/mTOR signaling alteration | Reduces sphere-forming ability and sensitizes OS cells to chemotherapeutic agents | [40, 41] |
| Bufalin | miR-148a/DNMT1/CDKN1B | Inhibits differentiation and proliferation of OS-sarcospheres | [42, 43] |
| Salinomycin | WNT signaling downregulation | Reduces sphere-formation and tumor-initiation ability of OS cells and sensitizes them to chemotherapeutic drugs | [44] |
| Salinomycin-loaded nanoparticles | — | When combined with CD133 aptamers selectively targets OS-CD133+ cells | [45] |
| Diallyl trisulfide | Upregulation of tumor-suppressive miRNAs/inhibition of NOTCH1 signaling/downregulation of ABCB1 | Prevents invasion, angiogenesis, and drug resistance in OS cells and in combination with methotrexate reduces OS-CD133+ cells | [46, 47] |
| MC1742/MC2625 | Histone deacetylase inhibition | Induces apoptosis and promotes differentiation of sarcoma CSCs | [48] |
| Vorinostat | Histone deacetylase inhibition | Reduces metastatic potential of OS cells | [49] |
| Anti-CD47 antibody | Increased macrophage phagocytosis | Inhibits invasion and metastasis of OS cells | [50] |
CDK6: cyclin-dependent kinase 6; IL6: interleukin 6; TGF-β: transforming growth factor β; YB-1: Y box-binding protein 1; HIF-2α: hypoxia inducible factors 2α; AMPK: AMP-activated protein kinase; mTOR: mechanistic target of rapamycin; DNMT1: DNA (cytosine-5-)-methyltransferase 1; CDKN1B: cyclin-dependent kinase inhibitor 1B; WNT: wingless-type MMTV integration site family; ABCB1: ATP-binding cassette subfamily B member 1.