Table 2.

Effects of aprepitant in AML cells.

In a dose-dependent manner exerts cytotoxic/antiproliferative effects and decreases AML cell survival/proliferative potential

Increases p73/p21 expression and alters cell cycle/DNA replication rate

Activates caspase-3-dependent apoptotic pathway

Aprepitant-ATO increase the number of AML apoptotic cells when compared to aprepitant alone

Aprepitant-ATO accumulate AML cells in sub-G1 phase and decrease DNA synthesis

Sensitizes AML cells to ATO via suppression of anti-apoptotic target genes of NF-κB

Aprepitant-ATO increase mRNA expression of pro-apoptotic targets (Bax, Bid, Bad, p21, p73)

Aprepitant-ATO decrease the expression of c-myc and regulates NF-κB activity

Diminished antitumor effect when the NF-κB pathway is overactivated

AML xenograft model: fosaprepitant increases the median survival 4–7 days

Induces AML cell death by apoptosis

A high dose of aprepitant does not affect lymphocytes proliferation

Exerts a higher damage in AML cells than in non-cancer cells

Blocks the formation of colonies of AML cells (size, circularity, perimeter)

Necrotic mechanisms are observed in AML cells upgrading aprepitant concentration

Increases mitochondrial reactive oxygen species

Mitochondrial oxidative stress is due to Ca++ flux from endoplasmic reticulum to mitochondria

Exerts an antinociceptive effect in myeloid leukemia-induced bone pain

Increases the level of apoptotic markers (annexin-V/propidium iodide)

Increases G0/G1 phase and decreases cells in S phase

No effect on human normal hematopoietic cells and no hemolytic toxicity on red blood cells