<p>Curcumin Combined with Thalidomide Reduces Expression of <em>STAT3</em> and <em>Bcl-xL</em>, Leading to Apoptosis in Acute Myeloid Leukemia Cell Lines</p>

Abstract

Introduction: Acute myeloid leukemia (AML) is a type of blood disorder that exhibits uncontrolled growth and reduced ability to undergo apoptosis. Signal transducer and activator of transcription 3 (STAT3) is a family member of transcription factors which promotes carcinogenesis in most human cancers. This effect on AML is accomplished through deregulation of several critical genes, such as B cell lymphoma-extra-large (BCL-XL) which is anti-apoptotic protein. The aim of this study was to evaluate the effect of curcumin (CUR) and thalidomide (THAL) on apoptosis induction and also the alteration of the mRNA expression level of STAT3 and BCL-XL mRNA on AML cell line compounds. Methods: The growth inhibitory effects of CUR and THAL and their combination were measured by MTT assay in U937 and KG-1 cell lines. The rates of apoptosis induction and cell cycle analysis were measured by concurrent staining with Annexin V and PI. The mRNA expression level of STAT3 and BCL-XL was evaluated by Real-Time PCR. Results: CUR inhibited proliferation and induced apoptosis in both KG-1 and U937 cells and this effect increased by combination with THAL. The expression level of STAT3 and BCL-XL was significantly down-regulated in KG-1 cells after treatment by CUR and THAL and their combination. Conclusion: Overall, our findings suggested that down-regulation of STAT3 and BCL-XL mRNA expression in response to CUR and THAL treatment lead to inhibition of cell growth and induction of apoptosis.

Curcumin promotes cell cycle arrest and apoptosis of acute myeloid leukemia cells by inactivating AKT

“…Phytochemicals, which are natural compounds from plants, have been recognized as vital resources for novel drugs ( 5 ). For example, curcumin ( 6 ), epigallocatechin gallate (EGCG) ( 7 ), genistein ( 8 ) and resveratrol ( 9 ) have been reported to possess anti-AML properties. Curcumin is the main polyphenol component extracted from rhizomes of the plant Curcuma longa , and its therapeutic benefit has been demonstrated in various cancer types, including AML ( 10 ).…”

Natural biomolecules and derivatives as anticancer immunomodulatory agents

“…Curcumin/IFN-b/retinoic acid combination also showed synergistic antiproliferative effects by suppressing STAT3, Bcl-2, COX-2, MMP-9 and survivin, but upregulating GADD153 and GRIM-19 (272). Similarly in haematological malignancies curcumin has decreased STAT3 activation in multiple myeloma cells, acute myeloid leukaemia and chronic myelogenous leukemia (273)(274)(275). Curcumin also establishes a tumorsuppressive TME by TAM and CTL repolarization.…”

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy

“…Curcumin, its derivatives, and various curcumin-based nano-systems have also been studied for the antineoplastic activity [ 46 , 47 ]. Curcumin alone and combined with thalidomide reduces the expression of STAT3 and Bcl-xL, leading to apoptosis in acute myeloid leukemia cell lines [ 48 ]. Curcumin upregulates the death receptors’ expression [ 49 ].…”