Curcumin induces apoptosis in JAK2‐mutated cells by the inhibition of JAK2/STAT and mTORC1 pathways

Abstract

Myeloproliferative neoplasms are chronic myeloid cancers divided in Philadelphia positive and negative. The JAK2 V617F is the most common mutation in Philadelphia negative patients and results in a constitutive activation of the JAK/STAT pathway, conferring a proliferative advantage and apoptosis inhibition. Recent studies identified a functional crosstalk between the JAK/STAT and mTOR pathways. The identification of an effective therapy is often difficult, so the availability of new therapeutic approaches might be attractive. Previous studies showed that curcumin, the active principle of the Curcuma longa , can suppress JAK2/STAT pathways in different type of cancer and injuries. In this study, we investigated the anti‐proliferative and pro‐apoptotic effects of curcumin in JAK2 V617F‐ mutated cells. HEL cell line and cells from patients JAK2 V617F mutated have been incubated with increasing concentrations of curcumin for different time. Apoptosis and proliferation were evaluated. Subsequently, JAK2/STAT and AKT/mTOR pathways were investigated at both RNA and protein levels. We found that curcumin induces apoptosis and inhibition of proliferation in HEL cells. Furthermore, we showed that curcumin inhibits JAK2/STAT and mTORC1 pathways in JAK2 V617F‐ mutated cells. This inhibition suggests that curcumin could represent an alternative strategy to be explored for the treatment of patients with myeloproliferative neoplasms.

Impact of Host, Lifestyle and Environmental Factors in the Pathogenesis of MPN

“…Resveratrol is a naturally occurring plant-derived polyphenol and resveratrol treatment increased bone marrow HSPCs [76] as well as protected HSCs from radiation induced injury [77]. Curcumin treatment in vitro induced apoptosis in leukocytes from JAK2 V617F positive MPN patients [78]. These compounds are known for their anti-inflammatory properties and could have potentially beneficial effects in lowering the risk for MPN.…”

Curcumin downregulates the PI3K–AKT–mTOR pathway and inhibits growth and progression in head and neck cancer cells

“…In a systematic review regarding the effects of curcumin on in vitro and in vivo HNC models, curcumin was reported to significantly reduce cell viability and tumor growth, inhibit cell proliferation, and induce cell cycle arrest and apoptosis (Borges et al, 2017). Recent studies showed that curcumin inhibited the activity of the mTOR complex 1 (mTORC1) on erythroleukemia cell lines (Petiti et al, 2019) and significantly decreased the expression and phosphorylation of AKT and mTOR on lung cancer (Liu et al, 2018) and ovarian cancer cells (Liu et al, 2019). It also reduced the phosphorylated levels of the downstream effectors ribosomal protein S6 kinase (p70 S6K) and 4E‐binding protein 1 (4E‐BP1) on ovarian cancer cells (Liu et al, 2019).…”

Genetic Screening for Potential New Targets in Chronic Myeloid Leukemia Based on Drosophila Transgenic for Human BCR-ABL1

“…White blood cells were separated by buffy coat, and total RNA was extracted using standard procedures. Expression levels of RAB5A and the housekeeping gene GUSB were evaluated by Real-Time PCR (qRT-PCR) using specific primers and probes assays (Hs00939627_m1 for GUSB and Hs00991290_m1 for RAB5A, Applied Biosystems and Thermo Fisher Scientific, Waltham, MA, USA) according to the published methods [ 33 ].…”