Table 1.
Mechanism of action of various natural products on AML stem cell population
| Compounds | Class of compound | Target and mechanism | Reference |
|---|---|---|---|
| Parthenolide | Sesquiterpene lactone | AML progenitors and CD34+/CD38- stem cell population. In vivo and in vitro. Inhibition of NF-κB, activation of tumor suppressor p53, and increased production of reactive oxygen species (ROS). | [27] |
| Triptolide | Diterpenoid triepoxide | CD34+/CD38- stem-like cells derived from KG1a cell line. In vivo and in vitro. Generation of ROS, downregulation of Nrf2 and HIF-1α pathways. |
[87] |
| Cantharidin | Terpene | Primary AML stem (CD34+) and progenitor cells. In vivo and in vitro. Modulate expression of genes involved in survival pathways (HLF, SLUG, NFIL3 and c-myc), induces p53 and mitochondrial-caspase cascade. |
[89] |
| Cyclopamine | Steroidal jerveratrum alkaloid | CD34+ cell lines and primary CD34+ AML stem cells. Inhibition of aberrantly activated hedgehog pathway and Bcl-2 expression. |
[56] |
| Salinomycin | Monocarboxylic polyether antibiotic | CD34+ CD38− KG1a AML SCs expressing functional ABC transporters P-glycoprotein, ABCG2, and ABCC11. In vitro. Overcomes ABC transporter-mediated multidrug and apoptosis resistance. |
[93] |
| 17-N-allylamino-17-demethoxy geldanamycin (17-AAG) | Geldanamycin derivative | Human AML CSCs (CD34+ CD38−) and murine lymphoma CSCs (c-Kit+Sca1+). In vitro. Induce apoptosis and eliminate the colony formation capacity by disrupting the transcriptional function of HIF1α. |
[95] |
| Kinetin riboside | Cytokinin | CD34+CD38− cell fraction present in primary AML samples. In vivo and in vitro. Induces apoptosis in LSCs and prevents AML stem cell engraftment in NOD/SCID mouse model. Adenosine kinase activity is required for the anti LSC effect. |
[99] |
| Resveratrol | Polyphenolic phytoalexin | AML stem-like KG1a cells. In vitro. Upregulate expressions of NKG2D ligands (ULBP1, ULBP2 and ULBP3) and TRAIL receptor 1 leading to enhanced cytokine-induced killer cell-mediated cytolysis. |
[102] |
| Avocatin B | 17-Carbon lipid | Primary AML stem (CD34+) and CD34+ cell lines. In vivo and in vitro. Generation of ROS, mitochondria-mediated apoptosis, characterized by the release of apoptosis inducing factor and cytochrome c. |
[104] |