Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing ubiquitin/proteasome-mediated cFos protein degradation

Ji, Lili; Zheng, Zhiyong; Shi, Liang; Huang, Yinjie; Lü, Bin; Wang, Zhengtao

doi:10.1016/j.bbagen.2015.01.005

Cited by 21 publications

(16 citation statements)

References 42 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ChIP was performed using the Magna ChIP G kit (Millipore) with minor modifications according to the protocol published elsewhere [ 46 ]. Briefly, primary T cells were unstimulated or activated with anti-CD3/CD28 or PMA/ionomycin, fixed with 1% formaldehyde, and sonicated, and immunoprecipitation was performed with rabbit IgG control or rabbit anti-c-Fos antibody [ 47 ]. The coimmunoprecipitated DNA served as a template for subsequent PCR with primers encompassing the NFAT2 promoter: Fwd: 5′-TGA TGT CAC TGA AGG GAG GG-3′ and Rev: 5′-GGA GCC TCT CGG TCT CAC TCT G-3′).…”

Section: Methodsmentioning

confidence: 99%

Unique properties of TCR-activated p38 are necessary for NFAT-dependent T-cell activation

et al. 2018

View full text Add to dashboard Cite

Nuclear factor of activated T cells (NFAT) transcription factors are required for induction of T-cell cytokine production and effector function. Although it is known that activation via the T-cell antigen receptor (TCR) results in 2 critical steps, calcineurin-mediated NFAT1 dephosphorylation and NFAT2 up-regulation, the molecular mechanisms underlying each are poorly understood. Here we find that T cell p38, which is activated by an alternative pathway independent of the mitogen-activated protein (MAP) kinase cascade and with different substrate specificities, directly controls these events. First, alternatively (but not classically) activated p38 was required to induce the expression of the AP-1 component c-Fos, which was necessary for NFAT2 expression and cytokine production. Second, alternatively (but not classically) activated p38 phosphorylated NFAT1 on a heretofore unidentified site, S79, and in its absence NFAT1 was unable to interact with calcineurin or migrate to the nucleus. These results demonstrate that the acquisition of unique specificities by TCR-activated p38 orchestrates NFAT-dependent T-cell functions.

show abstract

Section: Methodsmentioning

confidence: 99%

Unique properties of TCR-activated p38 are necessary for NFAT-dependent T-cell activation

et al. 2018

View full text Add to dashboard Cite

show abstract

“…VEGF/VEGFR2 signaling is considered as an important therapeutic target for the treatment of pathogenic angiogenesis because it is a predominant mediator of vasculogenesis and angiogenesis by induction of multiple signaling cascades (Olsson et al, 2006;Meissner et al, 2009). It has been reported that AD decreases VEGFD expression in hepatoma cancer cells (Ji et al, 2015) and both AD and its derivative A5 have been revealed to inhibit tumor angiogenesis via blocking VEGF-induced activation of VEGFR2 and its downstream MAPKs signaling pathways (Gong et al, 2013;Shen et al, 2014). Here, we found that ADN-9 was more powerful than AD in down-regulating VEGF expression and blocking VEGF-induced activation of VEGFR2, resulting in enhanced inactivation of multiple intracellular signaling cascades in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

“…f.), a traditional herbal medicine with multiple pharmacological functions, has attracted considerable attentions owing to the moderate cytotoxic effects on several cancer cell lines, as well as its inhibitory activity against migration and invasion in a variety of human cancer cells (Tzeng et al, 2012;Lai et al, 2013;Preet et al, 2014;Wong et al, 2016). Furthermore, it is proved that AD is effective in inhibiting tumor growth and attenuating tumor-associated neoangiogenesis in vivo (Nateewattana et al, 2014;Shen et al, 2014;Ji et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

In vivo inhibitory activity of andrographolide derivative ADN-9 against liver cancer and its mechanisms involved in inhibition of tumor angiogenesis

Yang

Zhao

Wang³

et al. 2017

Toxicology and Applied Pharmacology

View full text Add to dashboard Cite

It is well known that liver cancer is a highly aggressive malignancy with poor prognosis. Andrographolide (AD), a major bioactive component of Andrographis paniculata (Burm. F.), is a potential anti-cancer pharmacophore and the synthesis of AD derivatives with better cytotoxicity to cancer cells has attracted considerable attentions. In the present study, we evaluated the in vivo inhibitory effects of ADN-9, a 15-benzylidene substituted derivative of AD, on the growth and metastasis of murine hepatoma H22 using an orthotopic xenograft model and a subcutaneous xenograft model, and we further studied the anti-angiogenic action and the related mechanisms of ADN-9 in vivo and in vitro. Importantly, ADN-9 remarkably suppressed the growth and metastasis of both orthotopic and subcutaneous xenograft tumors, and the serum AFP level in orthotopic hepatoma-bearing mice treated with 100mg/kg ADN-9 (ig.) was decreased to the normal level. We also found that ADN-9 showed stronger abilities than AD in shrinking tumors, suppressing the invasion and metastasis of H22 cells, decreasing the MVD and promoting tumor cell apoptosis in subcutaneous xenograft of mice. Additionally, ADN-9 exhibited stronger inhibitory activity than AD against the migration and VEGF-induced capillary-like tube formation in HUVECs, which was further proved to be associated with attenuating VEGF/VEGFR2/AKT signaling pathway. The present research provides the first evidence that a 15-substituted AD derivative is more promising than the parent compound in therapeutic treatment of liver cancer.

show abstract

“…SP600125, an inhibitor of C-Jun N-terminal kinase (JNK), reversed the decreased expression of cFOS and VEGFD induced by andrographolide. 40…”

Section: Anticancer Activitymentioning

confidence: 99%

A Prospective Review on Phyto-Pharmacological Aspects of Andrographis paniculata

G¹,

Anand²,

Sampathkumar³

et al. 2018

SRP

View full text Add to dashboard Cite

Andrographis paniculata Nees is an annual herbaceous plant which belongs to the family Acanthaceae. It is commonly known as Kalmegh, is found in the plains of India, China, Pakistan, Sri Lanka and South Asia and is native to India and Sri Lanka. Kalmegh is known to be the "king of bitters" though it is of small size and it also has a similar appearance and taste as that of the Neem plant. It is one of the widely used effective medicinal plants in the world. All parts of this plant are used to extract the potential phytochemical, but the composition of phytoconstituents mostly differs from one part to another in a season, place and time of harvest. It is a traditional medicinal plant widely used in the treatment of anti-inflammatory, anti-bacterial, anti-oxidant, hepatoprotective, hematocidal, anti-HIV, anticancer, anti-diabetic, arthritis, rheumatism, cough, cold, multiple sclerosis, depression, diarrhoea, dysentery, candida, fevers, herpes, leprosy, malaria, jaundice, tuberculosis and several infectious diseases ranging from malaria to dysentery. The plant is widely used in Ayurvedic and homeopathic system of medicine. The medicinal value of this plant is due to the active ingredients via andrographolide and neoandrographolide, which are derivative of diterpinoids. It prevents oxidative damage and inhibits binding of toxic metabolite to DNA.

show abstract

Andrographolide decreased VEGFD expression in hepatoma cancer cells by inducing ubiquitin/proteasome-mediated cFos protein degradation

Cited by 21 publications

References 42 publications

Unique properties of TCR-activated p38 are necessary for NFAT-dependent T-cell activation

Unique properties of TCR-activated p38 are necessary for NFAT-dependent T-cell activation

In vivo inhibitory activity of andrographolide derivative ADN-9 against liver cancer and its mechanisms involved in inhibition of tumor angiogenesis

A Prospective Review on Phyto-Pharmacological Aspects of Andrographis paniculata

Contact Info

Product

Resources

About