Abstract:
:Autophagy, a form of cellular self-digestion by lysosome, is associated with various disease processes including cancers, and modulating autophagy has shown promise in the treatment of various malignancies. A number of natural products display strong antitumor activity, yet their mechanisms of action remain unclear. To gain a better understanding of how traditional Chinese medicine agents exert antitumor effects, we screened 480 natural compounds for their effects on autophagy using a high content screening assay detecting GFP-LC3 puncta in HeLa cells. Tubeimoside-1 (TBMS1), a triterpenoid saponin extracted from Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), was identified as a potent activator of autophagy. The activation of autophagy by TBMS1 was evidenced by increased LC3-II amount and GFP-LC3 dots, observation of autophagosomes under electron microscopy, and enhanced autophagic flux. To explore the mechanisms underlying TBMS1-activated autophagy, we performed cheminformatic analyses and surface plasmon resonance (SPR) binding assay that showed a higher likelihood of the binding between Akt protein and TBMS1. In three human breast cancer cell lines, we demonstrated that Akt-mTOR-eEF-2K pathway was involved in TBMS1-induced activation of autophagy, while Akt-mediated downregulations of Mcl-1, Bcl-xl, and Bcl-2 led to the activation of apoptosis of the breast cancer cells. Inhibition of autophagy enhanced the cytotoxic effect of TBMS1 via promoting apoptosis. Our results demonstrate the role and mechanism of TBMS1 in activating autophagy, suggesting that inhibition of cytoprotective autophagy may act as a therapeutic strategy to reinforce the activity of TBMS1 against cancers.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Jiang SL,Guan YD,Chen XS,Ge P,Wang XL,Lao YZ,Xiao SS,Zhang Y,Yang JM,Xu XJ,Cao DS,Cheng Ydoi
10.1038/s41401-018-0165-9subject
Has Abstractpub_date
2019-07-01 00:00:00pages
919-928issue
7eissn
1671-4083issn
1745-7254pii
10.1038/s41401-018-0165-9journal_volume
40pub_type
杂志文章abstract:AIM:To determine whether ONO-1078 (pranlukast), a potent leukotriene receptor antagonist, has neuroprotective effect on focal cerebral ischemia in the rat. METHODS:Focal cerebral ischemia was induced by 30 min of middle cerebral artery (MCA) occlusion and followed by 24 h reperfusion. ONO-1078 (0.003-1.0 mg/kg) or veh...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
abstract::Recent evidence shows that raddeanin A (RA), an oleanane-type triterpenoid saponin extracted from Anemone raddeana Regel, exerts remarkable cytotoxicity against cancer cells in vitro and in vivo. In addition, RA has also been found to activate autophagy in human gastric cancer cells. In this study, we investigated the...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2017.139
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abstract:AIM:To study the protective effect of the polypeptide isolated from Chlamys farreri (PCF) on hairless mice skin damaged by ultraviolet A. METHODS:Enzymes and malondialdehyde (MDA) were determined by biochemical methods; the expressions of Bcl-2 protein and NOS protein were examined by immunohistochemical technique. Th...
journal_title:Acta pharmacologica Sinica
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abstract::Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), a rapidly progressing clonal malignancy of CD4+ T lymphocytes. Exploring the host-HTLV-1 interactions and the molecular mechanisms underlying HTLV-1-mediated tumorigenesis is critical for developing efficien...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
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abstract::Retinoid X receptor-α (RXRα), a unique member of the nuclear receptor superfamily, represents an intriguing and unusual target for pharmacologic interventions and therapeutic applications in cancer, metabolic disorders and neurodegenerative diseases. Despite the fact that the RXR-based drug Targretin (bexarotene) is c...
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pub_type: 杂志文章,评审
doi:10.1038/aps.2014.109
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abstract::Resibufogenin (RBG) is a single compound isolated from Chansu, a traditional Chinese medicine obtained from the skin venom gland of the toad. Formulations of Chansu have been widely applied in China, Japan, and other Asian countries for a long time and are currently used as alternative medicines. However, there have b...
journal_title:Acta pharmacologica Sinica
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doi:
更新日期:2001-04-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-10-01 00:00:00
abstract::Due to the lack of typical clinical symptoms, the average delay time for diagnosis of pulmonary hypertension (PH) is longer than 2 years. It is urgent to find biomarkers for PH diagnosis. In this study we investigated whether plasma microRNAs (miRNAs) can be used as biomarkers for PH diagnosis. We used microarray to i...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2018.39
更新日期:2018-07-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-03-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.1
更新日期:2009-03-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00485.x
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2000-09-01 00:00:00
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更新日期:2007-09-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
doi:10.1038/aps.2009.47
更新日期:2009-06-01 00:00:00
abstract::The therapeutic outcome of chemotherapy is severely limited by intrinsic or acquired drug resistance, the most common causes of chemotherapy failure. In the past few decades, advancements in nanotechnology have provided alternative strategies for combating tumor drug resistance. Drug-loaded nanoparticles (NPs) have se...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
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更新日期:2017-01-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2006.00365.x
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
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journal_title:Acta pharmacologica Sinica
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journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:2002-08-01 00:00:00
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更新日期:2001-02-01 00:00:00
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doi:10.1111/j.1745-7254.2007.00536.x
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
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更新日期:2021-01-25 00:00:00
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更新日期:2000-10-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2006-11-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 临床试验,杂志文章
doi:
更新日期:2001-01-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2014.164
更新日期:2015-04-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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更新日期:2012-04-01 00:00:00