Curcumin reduces the expression of survivin, leading to enhancement of arsenic trioxide-induced apoptosis in myelodysplastic syndrome and leukemia stem-like cells

Abstract

Low response, treatment-related complications and relapse due to the low sensitivity of myelodysplastic syndrome (MDS) and leukemia stem cells (LSCs) or pre-LSCs to arsenic trioxide (ATO), represent the main problems following treatment with ATO alone in patients with MDS. To solve these problems, a chemosensitization agent can be applied to increase the susceptibility of these cells to ATO. Curcumin (CUR), which possesses a wide range of anticancer activities, is a commonly used chemosensitization agent for various types of tumors, including hematopoietic malignancies. In the present study, we investigated the cytotoxic effects and potential mechanisms in MDS-SKM-1 and leukemia stem-like KG1a cells treated with CUR and ATO alone or in combination. CUR and ATO exhibited growth inhibition detected by MTT assays and apoptosis analyzed by Annexin V/PI analyses in both SKM-1 and KG1a cells. Apoptosis of SKM-1 and KG1a cells determined by Annexin V/PI was significantly enhanced in the combination groups compared with the groups treated with either agent alone. Further evaluation was performed by western blotting for two hallmark markers of apoptosis, caspase-3 and cleaved-PARP. Co-treatment of the cells with CUR and ATO resulted in significant synergistic effects. In SKM-1 and KG1a cells, 31 and 13 proteins analyzed by protein array assays were modulated, respectively. Notably, survivin protein expression levels were downregulated in both cell lines treated with CUR alone and in combination with ATO, particularly in the latter case. Susceptibility to apoptosis was significantly increased in SKM-1 and KG1a cells treated with siRNA-survivin and ATO. These results suggested that CUR increased the sensitivity of SKM-1 and KG1a cells to ATO by downregulating the expression of survivin.

Pharmacogenomic Characterization and Isobologram Analysis of the Combination of Ascorbic Acid and Curcumin—Two Main Metabolites of Curcuma longa—in Cancer Cells

“…If applied alone, curcumin and AA were cytotoxic toward cell lines of different tumor types with curcumin exhibiting stronger cytotoxicity than AA. Our results are in line with other reports on the inhibitory activity of curcumin (Bimonte et al, 2016 ; Guzzarlamudi et al, 2016 ; Kasi et al, 2016 ; Ye et al, 2016 ; Yu et al, 2016 ; Zeng et al, 2016 ) and AA (Chen et al, 2015 ; Fukui et al, 2015 ; Jacobs et al, 2015 ; Sunil Kumar et al, 2015 ; Venturelli et al, 2015 ). The anticancer effects of curcumin in vitro and in vivo are primarily due to the activation of apoptotic pathways in cancer cells as well as the inhibition of mechanisms related to the tumor microenvironments such as inflammation, angiogenesis, invasion, and metastasis.…”

Curcumin differentially affects cell cycle and cell death in acute and chronic myeloid leukemia cells

“…Curcumin is a natural bioactive compound which exerts antiproliferative and pro-apoptotic effects in a wide variety of cellular and animal cancer models. In fact, curcumin is being used as a radio and chemo-sensitizer in different types of cancer (28)(29)(30). However, several studies have shown that curcumin elicits different responses at the level of cell cycle regulation and cell death, depending upon the dose, time of exposure, and, perhaps most importantly, the tumor cell type.…”

Orf Virus Encoded Protein ORFV119 Induces Cell Apoptosis Through the Extrinsic and Intrinsic Pathways

“…For instance, the VSV-GFP virus activates apoptosis via both the intrinsic and extrinsic pathways in most PDAC cell lines, but only the intrinsic pathway in Capan-2 and AsPC-1 cell lines ( Felt et al, 2015 ). Earlier reports revealed pro- and anti-apoptotic proteins/drugs involved in the extrinsic, intrinsic and/or the ER stress pathway, such as Nsp4 and Nsp10 encoded by PRRSV ( Yuan et al, 2016 ), Curcumin ( Zeng et al, 2016 ), Goniothalamin ( Li et al, 2016 ). Several viruses, such as herpes simplex virus, Varicella zoster virus, rabies virus, human immunodeficiency virus, and reovirus, have been shown to induce apoptosis in susceptible cells ( Kennedy, 2015 ).…”