Alantolactone inhibits growth of K562/adriamycin cells by downregulating Bcr/Abl and P‐glycoprotein expression

Yang, Chunhui; Yang, Jingbo; Sun, Meiyan; Yan, Jiangzhou; Meng, Xiangjun; Ma, Tiantian

doi:10.1002/iub.1141

Cited by 25 publications

(38 citation statements)

References 39 publications

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“…Bcr-Abl is frequently the causative agent in CML and is known to be associated with drug resistance (1). It has been reported that SAHA enhances sensitivity to imatinib in CML cells by decreasing the level of the Bcr-Abl protein and that this effect is associated with apoptosis (8).…”

Section: Discussionmentioning

confidence: 99%

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Proteasome inhibitor MG-132 enhances histone deacetylase inhibitor SAHA-induced cell death of chronic myeloid leukemia cells by an ROS-mediated mechanism and downregulation of the Bcr-Abl fusion protein

Zhu

Xiao

et al. 2015

Oncology Letters

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Abstract.Recently, there has been progress in the treatment of chronic myeloid leukemia (CML). However, novel therapeutic strategies are required in order to address the emerging problem of imatinib resistance. Histone deacetylase inhibitors (HDACi) and proteasome inhibitors are promising alternatives, and may be amenable to integration with current therapeutic approaches. However, the mechanisms underlying the interaction between these two agents remain unclear. The present study assessed the cytotoxic effect of the HDACi, suberoylanilide hydroxamic acid (SAHA), in combination with the proteasome inhibitor, MG-132, in imatinib-sensitive K562 and imatinib-resistant K562G cells, and investigated the mechanism underlying this effect. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method and protein expression levels were determined by western blotting. Reactive oxygen species (ROS) generation levels were observed under a fluorescence microscope The results indicated that SAHA and MG-132 act in a synergistic manner to induce cell death in K562 and K562G cells. This effect was associated with Bcr-Abl downregulation and the production of ROS. Notably, the ROS scavenger, N-acetyl-L-cysteine, almost fully reversed the cell death and Bcr-Abl downregulation that was induced by the combination of SAHA and MG-132. By contrast, the pan-caspase inhibitor, z-VAD-fmk, only partially reversed the cell death induced by these two drugs in CML cells. These results indicated that increased intracellular ROS levels are important in the induction of cell death and the downregulation of Bcr-Abl. In conclusion, the present results suggested that combined SAHA and MG-132 may be a promising treatment for CML.

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Section: Discussionmentioning

confidence: 99%

“…Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder, characterized by the expression and abnormal tyrosine kinase activity of the Bcr-Abl protein (1). The current recommended first line therapy for patients with newly diagnosed CML, is imatinib.…”

Section: Introductionmentioning

confidence: 99%

Proteasome inhibitor MG-132 enhances histone deacetylase inhibitor SAHA-induced cell death of chronic myeloid leukemia cells by an ROS-mediated mechanism and downregulation of the Bcr-Abl fusion protein

Zhu

Xiao

et al. 2015

Oncology Letters

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“…It has also been documented that alantolactone significantly increased the expression of p53 in HepG2 cells (49,50) with concomitant increase of its downstream target genes, mainly cyclin-dependent kinase inhibitor p21 in adriamycin-resistant human erythroleukemia cell line K562/ADR (51). Alantolactone induces p53-independent apoptosis in prostate cancer PC-3 cells (52).…”

Section: P53 and Its Family Members Pathwaymentioning

confidence: 95%

“…Therefore, to arrest cancerous cell proliferation, regulation of apoptosis and its signaling pathways play a critical role (8,147,148). This behavior may lead to cellcycle arrest and upregulation of proapoptotic-related proteins expression (49)(50)(51). In addition, it also documented that the selected natural compounds induced cell-cycle arrest either G 2 -M, or S or G 0 -G 1 phase.…”

Section: Targeting Cancer Cells By Cell-cycle-mediated Apoptosis Pathwaymentioning

confidence: 96%

“…Various preclinical findings and results of several in vitro and in vivo studies convincingly argue for potent role of natural compounds in the prevention and treatment of many types of cancer. Many reports on mechanism of actions of the promising compounds target multiple signaling pathways, which vary widely depending on cancer origin (11,51).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

Millimouno

Dong

Liu

et al. 2014

Cancer Prevention Research

235

168

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Although the incidences are increasing day after day, scientists and researchers taken individually or by research group are trying to fight against cancer by several ways and also by different approaches and techniques. Sesquiterpenes, flavonoids, alkaloids, diterpenoids, and polyphenolic represent a large and diverse group of naturally occurring compounds found in a variety of fruits, vegetables, and medicinal plants with various anticancer properties. In this review, our aim is to give our perspective on the current status of the natural compounds belonging to these groups and discuss their natural sources, their anticancer activity, their molecular targets, and their mechanism of actions with specific emphasis on apoptosis pathways, which may help the further design and conduct of preclinical and clinical trials. Unlike pharmaceutical drugs, the selected natural compounds induce apoptosis by targeting multiple cellular signaling pathways including transcription factors, growth factors, tumor cell survival factors, inflammatory cytokines, protein kinases, and angiogenesis that are frequently deregulated in cancers and suggest that their simultaneous targeting by these compounds could result in efficacious and selective killing of cancer cells. This review suggests that they provide a novel opportunity for treatment of cancer, but clinical trials are still required to further validate them in cancer chemotherapy. Cancer Prev Res; 7(11);

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Alantolactone Induces Apoptosis and Cell Cycle Arrest on Lung Squamous Cancer SK‐MES‐1 Cells

Zhao

Pan

Luo

et al. 2015

J Biochem & Molecular Tox

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Alantolactone, a sesquiterpene lactone compound, has variety of pharmacological properties, including anti-inflammatory and antineoplastic effects. In our study, alantolactone inhibited cancer cell proliferation. To explore the mechanisms underlying its antitumor action, we further examined apoptotic cells and cell cycle distribution using flow cytometry analysis. Alantolactone triggered apoptosis and induced cell cycle G1/G0 phase arrest. Furthermore, the expressions of caspases-8, -9, -3, PARP, and Bax were significantly upregulated, while antiapoptotic factor Bcl-2 expression was inhibited. In addition, the expressions of cyclin-dependent kinase 4 (CDK4), CDK6, cyclin D3, and cyclin D1 were downregulated by alantolactone. Therefore, our findings indicated that alantolactone has an antiproliferative role on lung squamous cancer cells, and it may be a promising chemotherapeutic agent for squamous lung cancer SK-MES-1 cells.

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Alantolactone inhibits growth of K562/adriamycin cells by downregulating Bcr/Abl and P‐glycoprotein expression

Cited by 25 publications

References 39 publications

Proteasome inhibitor MG-132 enhances histone deacetylase inhibitor SAHA-induced cell death of chronic myeloid leukemia cells by an ROS-mediated mechanism and downregulation of the Bcr-Abl fusion protein

Proteasome inhibitor MG-132 enhances histone deacetylase inhibitor SAHA-induced cell death of chronic myeloid leukemia cells by an ROS-mediated mechanism and downregulation of the Bcr-Abl fusion protein

Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

Alantolactone Induces Apoptosis and Cell Cycle Arrest on Lung Squamous Cancer SK‐MES‐1 Cells

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