Down-Regulation of Mcl-1 by Small Interference RNA Induces Apoptosis and Sensitizes HL-60 Leukemia Cells to Etoposide

Karami, Hadi; Baradaran, Behzad; Esfehani, Ali Jafarzadeh; Sakhinia, Masoud; Sakhinia, Ebrahim

doi:10.7314/apjcp.2014.15.2.629

Cited by 23 publications

(13 citation statements)

References 33 publications

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“…MCL-1 is known as a tumor survival factor via suppressing the apoptosis by inhibiting the normal function of proapoptotic Bcl-2 family proteins such as Noxa [ 22 ]. Moreover, MCL-1 is reported to mediate chemotherapy resistance in multiple cancers [ 23 , 24 ]. In this study, we found that MCL-1 was significantly overexpressed in MCF-7/DOXR cells, suggesting that the MCL-1 might be essential for doxorubicin resistance in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1

Long

Jiang

et al. 2015

BioMed Research International

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MicroRNAs (miRNAs) family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of doxorubicin resistance is a common and critical limitation to cancer therapy. The aim of this study was to investigate whether miR-193b mediated the resistance of breast cancer cells to doxorubicin by targeting myeloid cell leukemia-1 (MCL-1). In this study, we found that miR-193b levels were significantly lower in doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells than in the parental MCF-7 cells. We observed that exogenous miR-193b significantly suppressed the ability of MCF-7/DOXR cells to resist doxorubicin. It demonstrated that miR-193b directly targeted MCL-1 3′-UTR (3′-Untranslated Regions). Further studies indicated that miR-193b sensitized MCF-7/DOXR cells to doxorubicin through a mechanism involving the downregulation of MCL-1. Together, our findings provide evidence that the modulation of miR-193b may represent a novel therapeutic target for the treatment of breast cancer.

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Section: Discussionmentioning

confidence: 99%

miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1

Long

Jiang

et al. 2015

BioMed Research International

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“…In similar study, Karami et al showed specific silencing of survivin expression by siRNA enhanced sensitivity of leukemic cells to etoposide. 29,30 In other studies, they showed MDR1 down-regulation synergistically increased the cytotoxic effects of oxaliplatin and etoposide on oxaliplatin resistant SW480 and etoposide resistant HL-60 cells.…”

Section: Discussionmentioning

confidence: 99%

Silencing of High Mobility Group Isoform I-C (HMGI-C) Enhances Paclitaxel Chemosensitivity in Breast Adenocarcinoma Cells (MDA-MB-468)

Mansoori¹,

Mohammadi²,

Goldar³

et al. 2016

Adv Pharm Bull

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“…Recent studies showed the inhibition of prosurvival BCL-2 family members by small interfering RNAs (siRNAs) could result in the induction of cells apoptosis and subsequently a reduction in tumor growth. For example, Specific down-regulation of Mcl-1 by siRNA induced significant apoptosis in leukemia cells in vitro (Karami et al, 2014). Furthermore, several microRNAs have been identified that regulate Bcl-2 expression.…”

Section: Targeting Anti-apoptotic Bcl-2 Family Membersmentioning

confidence: 99%

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

Goldar¹,

Khaniani²,

Derakhshan³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Programmed cell death (PCD) or apoptosis is a mechanism which is crucial for all multicellular organisms to control cell proliferation and maintain tissue homeostasis as well as eliminate harmful or unnecessary cells from an organism. Defects in the physiological mechanisms of apoptosis may contribute to different human diseases like cancer. Identification of the mechanisms of apoptosis and its effector proteins as well as the genes responsible for apoptosis has provided a new opportunity to discover and develop novel agents that can increase the sensitivity of cancer cells to undergo apoptosis or reset their apoptotic threshold. These novel targeted therapies include those targeting anti-apoptotic Bcl-2 family members, p53, the extrinsic pathway, FLICE-inhibitory protein (c-FLIP), inhibitor of apoptosis (IAP) proteins, and the caspases. In recent years a number of these novel agents have been assessed in preclinical and clinical trials. In this review, we introduce some of the key regulatory molecules that control the apoptotic pathways, extrinsic and intrinsic death receptors, discuss how defects in apoptotic pathways contribute to cancer, and list several agents being developed to target apoptosis.

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Down-Regulation of Mcl-1 by Small Interference RNA Induces Apoptosis and Sensitizes HL-60 Leukemia Cells to Etoposide

Cited by 23 publications

References 33 publications

miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1

miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1

Silencing of High Mobility Group Isoform I-C (HMGI-C) Enhances Paclitaxel Chemosensitivity in Breast Adenocarcinoma Cells (MDA-MB-468)

Molecular Mechanisms of Apoptosis and Roles in Cancer Development and Treatment

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