Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways

Ji, Lü; Zhong, Bing; Jiang, Xi; Mao, Fei; Liu, Gang; Song, Bin; Wang, Cheng Yuan; Jiao, Yongqin; Wang, Jiang Ping; Xu, Zhi; Li, Xing; Zhan, Bo

doi:10.18632/oncotarget.22274

Cited by 31 publications

(30 citation statements)

References 72 publications

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“…In control HL‐60 cells, CRT was mainly localised in the cytoplasm, but its expression was reduced and CRT translocated to the plasma membrane surface upon DADS treatment (Figure A). ROS generation is a crucial modulator in a variety of signaling pathways that are associated with autophagy and apoptosis . To measure ROS, we next used DCFH‐DA, which is rapidly oxidised to highly fluorescent dichlorofluorescein (DCF) in the presence of ROS.…”

Section: Resultsmentioning

confidence: 99%

Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

Sun

et al. 2018

J Cellular Molecular Medi

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Diallyl disulfide (DADS), the main active component of the cancer fighting allyl sulfides found in garlic, has shown potential as a therapeutic agent in various cancers. Previous studies showed DADS induction of HL‐60 cell differentiation involves down‐regulation of calreticulin (CRT). Here, we investigated the mechanism of DADS‐induced differentiation of human leukaemia cells and the potential involvement of CRT and CCAAT enhancer binding protein‐α (C/EBPα). We explored the expression of CRT and C/EBPα in clinical samples (20 healthy people and 19 acute myeloid leukaemia patients) and found that CRT and C/EBPα expressions were inversely correlated. DADS induction of differentiation of HL‐60 cells resulted in down‐regulated CRT expression and elevated C/EBPα expression. In severe combined immunodeficiency mice injected with HL‐60 cells, DADS inhibited the growth of tumour tissue and decreased CRT levels and increased C/EBPα in vivo. We also found that DADS‐mediated down‐regulation of CRT and up‐regulation of C/EBPα involved enhancement of reactive oxidative species. RNA immunoprecipitation revealed that CRT bound C/EBPα mRNA, indicating its regulation of C/EBPα mRNA degradation by binding the UG‐rich element in the 3′ untranslated region of C/EBPα. In conclusion, the present study demonstrates the C/EBPα expression was correlated with CRT expression in vitro and in vivo and the molecular mechanism of DADS‐induced leukaemic cell differentiation.

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Section: Resultsmentioning

confidence: 99%

Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

Sun

et al. 2018

J Cellular Molecular Medi

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“…Additionally, tumor microenvironment regulation through interferon signaling pathway was down-regulated ( Table 3 ). Available reports on breast and other cancers indicate that actein targets cell apoptosis 48, 50 , cell adhesion 49 and migration 49, 50 . This analysis showed actein to target oncogenic signalling pathways mainly regulating cell cycle, proliferation and apoptosis processes in this cell type.…”

Section: Discussionmentioning

confidence: 99%

A systems pharmacology approach to determine the mechanisms of action of pleiotropic natural products in breast cancer from transcriptome data

Odongo

Zergeroǧlu

Çakır

2020

Preprint

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7 Background 8 Plant-derived natural products possess poly-pharmacologic 9 mechanisms of action with good tolerability and thus are Results 1 The signalling pathways regulated by the pleiotropic effects of 2 Actein, Withaferin A, Indole-3-Carbinol and Compound 3 Kushen were found to be projected on a set of oncogenesis 4 processes at the transcriptomic level in different breast cancer 5 subtypes (triple negative, luminal A and HER2+). Notably, 6 these compounds indirectly regulated known oncogenes in the 7 different subtypes through their associated pathways in the 8 subnetworks.9

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“…5c, LY294002 with TS I significantly decreased Bcl-2 protein expression and significantly increased the cleaved PARP and Bax protein expression compared with TS I treatment alone. Furthermore, the ROS-mediated AKT signaling pathway has been reported to be an important regulator of apoptosis in cancer cells, and has been shown to affect cell proliferation (19,20). To elucidate the role of ROS production in the TS I-mediated inhibition of the AKT signaling pathway in U87 MG cells, the cells were treated with NAc for 1 h and subsequently treated with TS I (1.25 µM) for 12 h. As shown in Fig.…”

Section: Cell Cycle Assaymentioning

confidence: 99%

Tanshinone I induces apoptosis and protective autophagy in human glioblastoma cells via a reactive oxygen species‑dependent pathway

et al. 2020

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Glioma is the most common primary malignancy of the central nervous system and is associated with high mortality rates. despite the available treatment options including surgery, radiotherapy and chemotherapy, the median patient survival rate is low. Therefore, the development of novel anticancer agents for the treatment of glioma is urgently required. Tanshinone I (TS I) is a tanshinone compound that is isolated from danshen. Accumulating evidence indicates that TS I exhibits antiproliferative activity in a variety of cancer types. However, the role of TS I and its mechanism of action in human glioma remain to be elucidated. In the present study, the anticancer potential of TS I against human glioma U87 MG cells was investigated. The results indicated that TS I exerted a potential cytotoxic effect on human glioma U87 MG cells. TS I was found to induce cell proliferation, inhibition, cell cycle arrest, apoptosis and autophagy in U87 MG cells. Mechanistic experiments indicated that TS I activated endoplasmic reticulum (ER) stress and inhibited AKT signaling and apoptosis in human glioma U87 MG cells. Furthermore, the present study demonstrated that TS I induced protective autophagy in U87 MG cells. Additionally, ER stress and AKT signal-mediated apoptosis and protective autophagy were found to be induced by TS I via intracellular reactive oxygen species accumulation. The results of the present study demonstrated that TS I may be a potential anticancer drug candidate that may be of value in the treatment of human glioma.

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Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways

Cited by 31 publications

References 72 publications

Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

Diallyl disulfide down‐regulates calreticulin and promotes C/EBPα expression in differentiation of human leukaemia cells

A systems pharmacology approach to determine the mechanisms of action of pleiotropic natural products in breast cancer from transcriptome data

Tanshinone I induces apoptosis and protective autophagy in human glioblastoma cells via a reactive oxygen species‑dependent pathway

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