Tomentosin inhibits cell proliferation and induces apoptosis in MOLT-4 leukemia cancer cells through the inhibition of mTOR/PI3K/Akt signaling pathway.

Abstract

Leukemia is amongst the cancers accountable for substantial mortality around the world. Tomentosin is a bioactive compound with a pharmacological significance, and its anticancer property against human leukemiaMOLT-4 cell line has never been reported. Hence, the objective of this study was to explore the anticancer activity of tomentosin in MOLT-4 human leukemia cells. In the current investigation, the cytotoxic effects of tomentosin ensuing potent toxicity (IC50 : 10 µM) in MOLT-4 cells after incubation at 24 h have been presented. Furthermore, tomentosin triggered intracellular reactive oxygen species production and showed the induction of intrinsic/mitochondrial pathways in treated MOLT-4 cells, revealing a significant cytotoxicity activity. Also, fluorescent microscopic studies using acridine orange/ethidium bromide and propidium iodide staining confirmed the occurrence of apoptosis in tomentosin-treated MOLT-4 cells. Quantitative reverse transcription polymerase chain reaction presented a negative regulation of cyclin D1 and BcL-2 expression and a positive regulated BAX and caspase-3 messenger RNA expression in tomentosin-treated MOLT-4 cells. Tomentosin further inhibited the inflammatory transcription factors such as nuclear factor κB (NF-κB), tumor necrosis factor α, interleukin 1β (IL-1β), and IL-6. Additionally, inhibition of the m-TOR/PI3K/AKT protein expression by tomentosin in MOLT-4 cells was confirmed. Overall, these findings lead to a conclusion that tomentosin induces apoptosis in MOLT-4 cells through caspase-facilitated proapoptotic pathway, and inhibition of the NF-κB-stimulated Bcl-2 facilitated the antiapoptotic pathway.