CURCUMIN: A NEW THERAPEUTIC STRATEGY FOR JAK2 V617F MUTATED CELLS
Author(s): ,
Jessica Petiti
Affiliations:
Clinical and Biological Sciences,University of Turin,Orbassano,Italy
,
Valentina Rosso
Affiliations:
Clinical and Biological Sciences,University of Turin,Orbassano,Italy
,
Cristina Panuzzo
Affiliations:
Clinical and Biological Sciences,University of Turin,Orbassano,Italy
Daniela Cilloni
Affiliations:
Clinical and Biological Sciences,University of Turin,Orbassano,Italy
(Abstract release date: 05/17/18) EHA Library. Petiti J. 06/14/18; 216521; PB2272
Dr. Jessica Petiti
Dr. Jessica Petiti
Contributions
Abstract

Abstract: PB2272

Type: Publication Only

Background

The myeloproliferative neoplasms (MPNs) are chronic myeloid cancers divided in Philadelphia (Ph) positive, chronic myeloid leukemia, or negative: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Mutations in JAK2, MPL and CALR genes are the biological markers in the most of Ph negative patients. The single base JAK2 V617F mutation is most common, with an incidence of 95% in PV and 50-55% in ET and PMF patients. The JAK2 protein has tyrosine kinase activity and the gain-of-function V617F mutation results in a constitutive activation of the JAK/STAT pathway, conferring a proliferative advantage and apoptosis inhibitions. The understanding of the molecular pathogenesis of MPNs has prompted the development of targeted agents, such as JAK inhibitors.

Curcumin is the active phytochemical component isolated from the rhizome of the Curcuma longa plant. Curcumin is a highly pleiotropic molecule with multiple pharmacological effects, such as anti-inflammatory, anti-microbial, anti-oxidative and anti-proliferative activities. Extensive preclinical trials have indicated curcumin’s therapeutic potential against a wide range of human diseases. Furthermore, previous studies showed that curcumin can suppress JAK2/STAT3 signaling pathways in different type of cancer and injuries.

Aims

The purpose of the present study was to investigate anti-proliferative and pro-apoptotic effects of curcumin in MPNs, in particular in JAK2 V617F cell lines.

Methods

HEL cell line, JAK2 V617F mutated in homozygosis, has been incubated with different concentrations of curcumin at different time points. Then, apoptosis, proliferation and cell cycle were evaluated. Subsequently, fragmentation of DNA, JAK2/STAT and AKT/mTOR pathways were investigated at both RNA and protein levels. 

Results

We identified that curcumin induced apoptosis, cells cycle arrest and inhibition of proliferation in HEL cell lines. Furthermore, we showed JAK2/STAT and AKT/mTOR pathways are affected by curcumin treatments. 

Conclusion
This study evaluates curcumin treatment in JAK2 mutated cell line, suggesting that it could be useful in the future for treatment of JAK2 V617F mutated patients.

Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research

Keyword(s): Curcumin, Janus Kinase inhibitor, Myeloproliferative disorder

Abstract: PB2272

Type: Publication Only

Background

The myeloproliferative neoplasms (MPNs) are chronic myeloid cancers divided in Philadelphia (Ph) positive, chronic myeloid leukemia, or negative: polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). Mutations in JAK2, MPL and CALR genes are the biological markers in the most of Ph negative patients. The single base JAK2 V617F mutation is most common, with an incidence of 95% in PV and 50-55% in ET and PMF patients. The JAK2 protein has tyrosine kinase activity and the gain-of-function V617F mutation results in a constitutive activation of the JAK/STAT pathway, conferring a proliferative advantage and apoptosis inhibitions. The understanding of the molecular pathogenesis of MPNs has prompted the development of targeted agents, such as JAK inhibitors.

Curcumin is the active phytochemical component isolated from the rhizome of the Curcuma longa plant. Curcumin is a highly pleiotropic molecule with multiple pharmacological effects, such as anti-inflammatory, anti-microbial, anti-oxidative and anti-proliferative activities. Extensive preclinical trials have indicated curcumin’s therapeutic potential against a wide range of human diseases. Furthermore, previous studies showed that curcumin can suppress JAK2/STAT3 signaling pathways in different type of cancer and injuries.

Aims

The purpose of the present study was to investigate anti-proliferative and pro-apoptotic effects of curcumin in MPNs, in particular in JAK2 V617F cell lines.

Methods

HEL cell line, JAK2 V617F mutated in homozygosis, has been incubated with different concentrations of curcumin at different time points. Then, apoptosis, proliferation and cell cycle were evaluated. Subsequently, fragmentation of DNA, JAK2/STAT and AKT/mTOR pathways were investigated at both RNA and protein levels. 

Results

We identified that curcumin induced apoptosis, cells cycle arrest and inhibition of proliferation in HEL cell lines. Furthermore, we showed JAK2/STAT and AKT/mTOR pathways are affected by curcumin treatments. 

Conclusion
This study evaluates curcumin treatment in JAK2 mutated cell line, suggesting that it could be useful in the future for treatment of JAK2 V617F mutated patients.

Session topic: 15. Myeloproliferative neoplasms – Biology & Translational Research

Keyword(s): Curcumin, Janus Kinase inhibitor, Myeloproliferative disorder

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