Abstract:
:Hispidulin, a polyphenolic flavonoid extracted from the traditional Chinese medicinal plant S involucrata, exhibits anti-tumor effects in a wide array of human cancer cells, mainly through growth inhibition, apoptosis induction and cell cycle arrest. However, its precise anticancer mechanisms remain unclear. In this study, we investigated the molecular mechanisms that contribute to hispidulin-induced apoptosis of human clear-cell renal cell carcinoma (ccRCC) lines Caki-2 and ACHN. Hispidulin (10, 20 μmol/L) decreased the viability of ccRCC cells in dose- and time-dependent manners without affecting that of normal tubular epithelial cells. Moreover, hispidulin treatment dose-dependently increased the levels of cleaved caspase-8 and caspase-9, but the inhibitors of caspase-8 and caspase-9 only partly abrogated hispidulin-induced apoptosis, suggesting that hispidulin triggered apoptosis via both extrinsic and intrinsic pathways. Moreover, hispidulin treatment significantly inhibited the activity of sphingosine kinase 1 (SphK1) and consequently promoted ceramide accumulation, thus leading to apoptosis of the cancer cells, whereas pretreatment with K6PC-5, an activator of SphK1, or overexpression of SphK1 significantly attenuated the anti-proliferative and pro-apoptotic effects of hispidulin. In addition, hispidulin treatment dose-dependently activated ROS/JNK signaling and led to cell apoptosis. We further demonstrated in Caki-2 xenograft nude mice that injection of hispidulin (20, 40 mg·kg-1·d-1, ip) dose-dependently suppressed tumor growth accompanied by decreased SphK1 activity and increased ceramide accumulation in tumor tissues. Our findings reveal a new explanation for the anti-tumor mechanisms of hispidulin, and suggest that SphK1 and ceramide may serve as potential therapeutic targets for the treatment of ccRCC.
journal_name
Acta Pharmacol Sinjournal_title
Acta pharmacologica Sinicaauthors
Gao H,Gao MQ,Peng JJ,Han M,Liu KL,Han YTdoi
10.1038/aps.2017.154subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1618-1631issue
12eissn
1671-4083issn
1745-7254pii
aps2017154journal_volume
38pub_type
杂志文章abstract:AIM:To differentiate the electrophysiological characteristics of somatic action potentials (AP) from isolated Neo and Juv nodose sensory neurons (NSN) and those from slices of intact Juv and adult rat nodose ganglia. METHODS:For isolated cell recordings nodose ganglia from 3-8 d old Neo and 4 weeks old Juv rats were d...
journal_title:Acta pharmacologica Sinica
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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abstract::Androgen and androgen receptor (AR) signaling are crucial for the genesis of prostate cancer (PCa), which can often develop into androgen-ligand-independent diseases that are lethal to the patients. Recent studies show that even these hormone-refractory PCa require ligand-independent AR signaling for survival. As curr...
journal_title:Acta pharmacologica Sinica
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journal_title:Acta pharmacologica Sinica
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pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00611.x
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00581.x
更新日期:2007-07-01 00:00:00
abstract:AIM:Genetic variation in ALOX12, which encoded human 12-lipoxygenase, was found to be associated with fat mass in young Chinese men. The objective of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) and haplotypes in the ALOX15 gene and obesity-related phenotypes in Chinese ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2011.167
更新日期:2012-02-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.88
更新日期:2016-12-01 00:00:00
abstract:AIM:To study the effect of gum mastic, a natural resin, on the proliferation of androgen-independent prostate cancer PC-3 cells, and further investigate the mechanisms involved in this regulatory system, taking nuclear factor kappaB (NF-kappaB) signal as the target. METHODS:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltet...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00536.x
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pub_type: 杂志文章,评审
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
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abstract::Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservati...
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pub_type: 杂志文章
doi:10.1111/j.1745-7254.2007.00540.x
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journal_title:Acta pharmacologica Sinica
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doi:
更新日期:2004-07-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2004-05-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.7
更新日期:2016-05-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2010.83
更新日期:2010-08-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章,评审
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更新日期:2016-03-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2016.83
更新日期:2016-11-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1111/j.1745-7254.2005.00013.x
更新日期:2005-01-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-04-01 00:00:00
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journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:10.1038/aps.2009.13
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:
更新日期:2003-11-01 00:00:00
abstract:AIM:To study the effect of chronic insulin treatment on insulin post-receptor signaling transduction and whether the effects of metformin are transmitted throughout the cascade of insulin signaling intermediates in a human hepatoma cell line (Hep G2). METHODS:Hep G2 cells were incubated in serum free media containing ...
journal_title:Acta pharmacologica Sinica
pub_type: 杂志文章
doi:
更新日期:2003-01-01 00:00:00