Axolotl Ambystoma mexicanum extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells

Abstract

Acute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. Although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve patient outcome and minimize toxicity is needed. In this study, the antitumor activity of axolotl (AXO) Ambystoma mexicanum crude extract was assessed in vitro on the human acute myeloid leukemia HL-60 cell line. The anticancer activity was evaluated in terms of ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation. Moreover, gene expression analysis was performed to evaluate the genes involved in the regulation of these processes. The AXO crude extract exhibited antiproliferative but not cytotoxic activities on HL-60 cells, with cell cycle arrest in the G0/G1 phase. Furthermore, the AXO-treated HL-60 cells showed an increase in both the percentage of nitroblue tetrazolium positive cells and the expression of CD11b, whereas the proportion of CD14-positive cells did not change, suggesting that extract is able to induce differentiation toward the granulocytic lineage. Finally, the treatment with AXO extract caused upregulation of CEBPA, CEBPB, CEBPE, SPI1, CDKN1A, and CDKN2C, and downregulation of c-MYC. Our data clearly show the potential anticancer activity of Ambystoma mexicanum on HL-60 cells and suggest that it could help develop promising therapeutic agents for the treatment of acute myeloid leukemia.

Cancer in Amphibia, a rare phenomenon?

“…As suggested, it provides the signals required to carry out regeneration with no mistakes and it ensures the creation of the amputated limb, it also promotes a protective effect to strictly maintain genomic stability and functionality to minimize the risk of malignant transformations (Corradetti et al, 2021). As mentioned above, chemically cancer induction was unsuccessful in Urodela, consistent with this, it was shown recently that a total crude extract of axolotl made of amputated hindlimbs has anticancer activity on the in vitro human acute myeloid leukemia HL‐60 and Kg‐1a cell lines (Suleiman et al, 2020). This was evaluated in terms of the ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation.…”

“…The mean frequency of micronuclei observed with a concentration of 0.02 mg/L of 4NQO was 31.93% (le Curieux et al, 1992). However, in regeneration, the individual control Although the mechanisms through which amphibians resist cancer have not yet been elucidated, it is clear that in addition to the apparent relationship between regeneration and cancer, amphibians possess characteristics that could contribute to resistance to neoplasms such as the mentioned embryonic environment, the high immune reactivity to their altered self-antigenicity, which translates into difficulty in accepting cancer cells, the induction of dramatic apoptosis after exposure to mitogenic cancer-promoting reagents (Ruben et al, 2007(Ruben et al, , 2013, and the production of biologically active molecules with anticancer activities (Suleiman et al, 2020). Future research will shed light on cancer resistance using amphibian models as a starting point, for possible application in human medicine.…”

“…shown recently that a total crude extract of axolotl made of amputated hindlimbs has anticancer activity on the in vitro human acute myeloid leukemia HL-60 and Kg-1a cell lines (Suleiman et al, 2020). This was evaluated in terms of the ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation.…”

Axolotl: A resourceful vertebrate model for regeneration and beyond

“…Decreased tumorigenicity in breast cancer cells by AOE was associated with cell‐cycle arrest and quiescence as a consequence of decreased MAPK and increased pRB activities 122 . AOE was also studied in another cancer model, acute myeloid leukemia, and a time and dose dependent cell viability decrease characterized by cell cycle arrest at G0/G1 transition was observed 123 …”

“…122 AOE was also studied in another cancer model, acute myeloid leukemia, and a time and dose dependent cell viability decrease characterized by cell cycle arrest at G0/G1 transition was observed. 123 According to evolutionary biologists, the limited regeneration potential of higher organisms, including most mammals, is probably due to the trade-off between regenerative capacity and cancer development. The altered gene expression profile to stimulate proliferation, migration, and activation of progenitor cells during regeneration is quite risky and resembles the activities in tumors.…”