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Table 1 Mechanism of action of various natural products on AML stem cell population

From: Targeting acute myeloid leukemia stem cell signaling by natural products

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]