Indole-3-carbinol induces apoptosis of chronic myelogenous leukemia cells through suppression of STAT5 and Akt signaling pathways

Abstract

Signal transducer and activator of transcription 5 and Akt pathways, implicated in signaling transduction downstream of BCR-ABL, play critical roles in the pathogenesis of chronic myeloid leukemia. Therefore, identification of novel compounds that modulate the activity of such pathways could be a new approach in the treatment of chronic myeloid leukemia. Previous studies have demonstrated that indole-3-carbinol inhibits the proliferation and induces apoptosis of various tumor cells. However, its anticancer activity against chronic myeloid leukemia cells and the underlying mechanism remain unclear. Our data revealed that indole-3-carbinol promoted mitochondrial apoptosis of chronic myeloid leukemia-derived K562 cells, as evidenced by the activation of caspases and poly (ADP-ribose) polymerase cleavage. Treatment with indole-3-carbinol was found to be associated with a decrease in the cellular levels of phospho-Akt and phospho-signal transducer and activator of transcription 5. In addition, real-time polymerase chain reaction analysis showed that the downregulation of genes is regulated by Akt and signal transducer and activator of transcription 5. We also found that treatment with indole-3-carbinol resulted in the activation of the p38 mitogen-activated protein kinase and reduced expression of human telomerase and c-Myc. Collectively, these results demonstrate that the oncogenic signal transducer and activator of transcription 5/Akt pathway is a cellular target for indole-3-carbinol in chronic myeloid leukemia cells. Thus, this clinically tested natural compound can be a potential candidate in the treatment of chronic myeloid leukemia following confirmation with clinical studies.

Protective Effect of Indole-3-Carbinol on Sperm Morphometric Alteration in a High-Fat Diet-Induced Obese Rat Model

“…Antioxidants are substances that act as free radical scavengers and prevent cellular damage by reacting with free radicals. Indole-3-carbinol (I3C) is a phytochemical substance found in the plants of Cruciferae family, which is known as therapeutic agents due to substantial anticancer and antioxidant activity (9,10). I3C can also exert an ameliorative effect against inflammation in obese rats (11).…”

Dysregulation of LINC00470 and METTL3 promotes chemoresistance and suppresses autophagy of chronic myelocytic leukaemia cells

“…45 AKT can promote cell survival and growth by activating downstream targets including XIAP, Bcl-2, as well as surviving, which were shown to be linked to a poor prognosis YY. [46][47][48]…”

Telomerase Inhibition in the Treatment of Leukemia: A Comprehensive Review

“…The most effective concentration of I3C was 400 µM of the substance after 32 h; it has to be noted that 200 µM had no effect on c-Myc. The expression of c-Myc was measured after 18 and 32 h; however, 32 h of incubation proved to be more efficient [30].…”