CP + SAL Induce Apoptosis in KG1-a Cells: Insulin Modulation

July, 07, 2024 | AML (Acute Myeloid Leukemia), Leukemia

KEY TAKEAWAYS

  • The study aimed to assess whether CP + SAL induced apoptosis in KG1-a cells, modulated by insulin.
  • Researchers observed that CP + SAL treatment strongly impacted KG1-a cells; PI3K-Akt signaling was a key target.

Acute Myeloid Leukemia (AML) is a rapidly progressing cancer that affects the blood and bone marrow. It is characterized by the swift growth of abnormal white blood cells. Chemotherapeutic agents, the primary treatment for AML, face clinical challenges such as poor solubility and low bioavailability.

Previous research has shown that antibiotics can effectively induce cancer cell death and potentially prevent metastasis. Additionally, insulin is known to activate the PI3K/Akt pathway, which is often disrupted in cancers. This leads to increased cell survival and resistance to apoptosis.

Maitham Alhajamee and the team aimed to examine the anti-cancer impact of the antibiotics ciprofloxacin (CP) and salinomycin (SAL) (CP + SAL), both individually and in combination, on KG1-a cells in the presence and absence of insulin.

This was accomplished by exposing KG1-a cells to different doses of CP + SAL alone, in combination with ± insulin for 24-72 h while the MTT assay was used to evaluate the cell viability. Besides, apoptotic effects were examined using Hoechst staining and Annexin-V/PI flow cytometry. The expression levels of Bax, p53, BIRC5, Akt, PTEN, and FOXO1 were analyzed through Real-Time PCR.

Results revealed that CP + SAL demonstrated cytotoxic and notable pro-apoptotic effects on KG1-a cells by upregulating Bax and p53 and downregulating BIRC5, resulting in G0/G1 cell cycle arrest and inhibition of the PI3K-Akt signaling pathway.

The findings showed that the combination of CP + SAL promoted apoptosis in the KG1-a cell line by downregulating BIRC5 and Akt, as well as upregulating Bax, p53, PTEN, and FOXO1.

Additionally, the results strongly indicated that insulin effectively mitigates apoptosis by enhancing Akt expression and reducing FOXO1 and PTEN gene expression in cells treated with CP + SAL.

The study concluded that the combined treatment of CP + SAL exhibited a strong anti-cancer effect on leukemia KG1-a cells. Additionally, it was discovered that PI3K-Akt signaling can be regarded as a promising target in leukemia treatment, particularly in hyperinsulinemia.

The study did not receive any kind of funding or financial support.

Source: https://pubmed.ncbi.nlm.nih.gov/39002036/

Alhajamee M, Khalaj-Kondori M, Babaei E, et al. (2024). “A biochemical assessment of apoptosis-inducing impact of Salinomycin in combination with ciprofloxacin on human leukemia KG1-a stem-like cells in the presence and absence of insulin. Mol Biol Rep. 2024 Jul 13;51(1):807. doi: 10.1007/s11033-024-09768-z. PMID: 39002036.

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