Saponins from Rubus parvifolius L. Induce Apoptosis in Human Chronic Myeloid Leukemia Cells through AMPK Activation and STAT3 Inhibition

Ge, Yuqing; Xu, Xiaofeng; Yang, Bo; Chen, Zhe; Cheng, Rubin

doi:10.7314/apjcp.2014.15.13.5455

Cited by 14 publications

(14 citation statements)

References 29 publications

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“…Phytochemicals from dietary plants and other plant sources, including herbs are becoming increasingly important sources of anticancer drugs or compounds for cancer chemopreventive or adjuvant chemotherapy (23). The use of traditional Chinese herbs has exhibit beneficial effects in overcoming apoptosis resistance in pancreatic cancer (24).…”

Section: Discussionmentioning

confidence: 99%

Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway

Yang

Chen

et al. 2015

Molecular Medicine Reports

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Abstract. Pancreatic cancer remains a challenging disease worldwide. Cryptotanshinone (CPT) is one of the active constituents of Salvia miltiorrhiza Bunge and exhibits significant antitumor activities in several human cancer cells. However, the efficacy and molecular mechanism of CPT in pancreatic cancer remains to be elucidated. In the present study, the effect of CPT on the proliferation, apoptosis and cell cycle of human pancreatic cancer cell BxPC-3 cells was evaluated. The results demonstrated that CPT inhibited proliferation of the BxPC-3 cells in a concentration-dependent manner, and significantly induced cell apoptosis and cell cycle arrest. The protein levels of cleaved caspase-3, caspase-9 and poly ADP ribose polymerase were upregulated, while the levels of c-myc, survivin and cyclin D1 were downregulated following treatment with CPT. In addition, CPT decreased the activities of signal transducer and activator of transcription 3 (STAT3) and several upstream regulatory signaling pathways after 24 h. However, CPT only inhibited the phosphorylation of STAT3 Tyr705 within 30 min, without marked effects on the phosphorylation of the other proteins. These results suggested that the inhibition of STAT3 activity by CPT was directly and independent of the upstream regulators in human pancreatic cancer. The present study demonstrated that CPT exerts anticancer effects by inducing apoptosis and cell cycle arrest via inhibition of the STAT3 signaling pathway in human BxPC-3 cells.

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Section: Discussionmentioning

confidence: 99%

Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway

Yang

Chen

et al. 2015

Molecular Medicine Reports

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“…Therapeutically controlling STAT3 signaling using different natural phytochemicals although has shown promise [ 12 - 14 ] however it still needs a detailed research.…”

Section: Introductionmentioning

confidence: 99%

Rutin mediated targeting of signaling machinery in cancer cells

et al. 2014

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Progress in our understanding of molecular oncology has started to shed light on dysregulation of spatio-temporally controlled signaling pathways, inactivation of tumor suppressor genes, tumour and normal stem cell quiescence, overexpression of oncogenes, extracellular and stromal microenvironments, epigenetics and autophagy. Sequentially and characteristically it has been shown that cancer cells acquire the ability to escape from apoptotic cell death, proliferate uncontrollably, sustain angiogenesis and tactfully reconstitute intracellular pathways to avoid immune surveillance. We have attempted to provide a recent snapshot of most recent progress with emphasis on how rutin modulates wide ranging intracellular signaling cascades as evidenced by in-vitro and in-vivo research. It is worth describing that 'single-cell proteomics' analysis has further improved our understanding regarding intracellular signaling pathways frequently activated in cancer cells resistant to therapeutics and can provide biomarkers for cancer diagnosis and prognosis. Data obtained from preclinical studies will prove to be helpful for scientists to bridge basic and translational studies.

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“…In this work, model parameters were calculated from the experimental data obtained from IL-6 induced signaling pathways. Systems biology techniques were used to understand various components involved in reaction mechanism of this pathway and to predict the behavior of individual reaction components (Heinrich et al 2002 ; Papin et al 2005 ; Tyson et al 2003 ; Ge et al 2013 ). Deterministic rate laws have been used to simulate various chemical and biochemical reactions (Edda et al 2006 ; Tian and Song 2012 ; Klipp and Liebermeister 2006 ).…”

Section: Methodsmentioning

confidence: 99%

Effect of STAT3 inhibitor in chronic myeloid leukemia associated signaling pathway: a mathematical modeling, simulation and systems biology study

et al. 2016

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Chronic myeloid leukemia (CML) is a hematopoietic stem-cell disorder which proliferates due to abnormal growth of basophil cells. Several proangiogenic molecules have been reported to be associated in CML progression, including the hepatocyte growth factor (HGF). However, detail mechanism about the cellular distribution and function of HGF in CML is yet to be revealed. The proliferation of hematopoietic cells are regulated by some of the growth factors like interleukin 3 (IL-3), IL-6, erythropoietin, thrombopoietin, etc. In this study IL-6 pathways have been taken into consideration which induces JAK/STAT and MAPK pathways to decipher the CML progression stages. An attempt has been made to model these pathways with the help of ordinary differential equations (ODEs) and estimating unknown parameters through fminsearch optimization algorithm. Some of the specific component like STAT3, of the pathway has been analyzed in detail and their role in CML progression has been elucidated. The roles of STAT3 inhibitors into the treatment of CML have been thoroughly studied and optimum concentration of the inhibitors have been predicted.Electronic supplementary materialThe online version of this article (doi:10.1007/s13205-015-0357-7) contains supplementary material, which is available to authorized users.

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Saponins from Rubus parvifolius L. Induce Apoptosis in Human Chronic Myeloid Leukemia Cells through AMPK Activation and STAT3 Inhibition

Cited by 14 publications

References 29 publications

Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway

Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway

Rutin mediated targeting of signaling machinery in cancer cells

Effect of STAT3 inhibitor in chronic myeloid leukemia associated signaling pathway: a mathematical modeling, simulation and systems biology study

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