Effect of &lt;I&gt;Radix Trichosanthis&lt;/I&gt; and Trichosanthin on Hepatitis B Virus in HepG2.2.15 Cells

Wen, Doudou; Wang, Jianing; Yan, Huiwen; Chen, Jia; Xia, Kun; Liu, Jing; Zhang, Ailian

doi:10.1166/jnn.2015.9271

Cited by 12 publications

(9 citation statements)

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“…TCS was reported to have immune-regulatory activity. It could ablate the replication of human immunodeficiency virus (HIV) and herpes simplex virus type 1 (HSV-1) [ 4 , 5 ]. TCS is a potential antidote against some tumors as it could suppress the tumor cell growth in different ways.…”

Section: Introductionmentioning

confidence: 99%

The anti-cancerous activity of recombinant trichosanthin on prostate cancer cell PC3

Zhang

et al. 2016

Biol Res

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ContextTrichosanthin produced in the root tube of Trichosanthes kirilowii shows anti-tumor activity on a series of cancer cells including Hela, MCF-7, HL-60. But there is little information about its effect on the carcinogenesis of prostate cancer.ObjectiveThis work was designed to study the role of trichosanthin on prostate cancer cells PC3.Materials and methodsTrichosanthin was expressed in BL21 strain and purified by affinity chromatography. MTT assay was designed to determine the effect of trichosanthin on growth of PC3 cells at doses of 10, 20, 40, 60, 80, and 120 μg/ml. Then the effect of 50 μg/ml rTCS alone or combined with 2 μM IL-2 on PC3 cell proliferation was analyzed. And the mechanism of rTCS was studied by western blot. After that the in vivo effect of rTCS combined with IL-2 was explored in mice bearing PC3 xenograft tumor.ResultsTrichosanthin was successfully expressed in BL21 and purified by 100 mM imidazole. It was shown to inhibit proliferation of PC3 cells in a dose-dependent manner with IC50 50.6 μg/ml. When combined with cytokine IL-2, a significant synergic effect was obtained. The inhibition rate on PC3 was around 50 % in combination group while only 35.5 % in single rTCS group at 50 μg/ml. Further, the expression of full length caspase-8 and Bcl-2 decreased significantly while cleaved caspase-8 and Bax were up-regulated, which suggest that caspase-8-mediated apoptosis pathway may be activated by rTCS in PC3 cells. Moreover, our data demonstrated that tumor volume and tumor weight were significantly reduced in rTCS-treated or rTCS/IL-2-treated nude mice bearing PC3 xenograft tumor compared with control. And significant difference was also found between rTCS and rTCS/IL-2 group.ConclusionsThis study demonstrates that rTCS is a potential agent with high in vitro and in vivo anti-tumor activity on PC3 cells. And rTCS combined with IL-2 is a promising strategy in treating patients with prostate cancer in future.

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Section: Introductionmentioning

confidence: 99%

The anti-cancerous activity of recombinant trichosanthin on prostate cancer cell PC3

Zhang

et al. 2016

Biol Res

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“…The plant Trichosanthes kirilowii has a long history of clinical use for treating hepatitis B virus (HBV) in China. As the main component in the aqueous extract of Trichosanthis Radix, TCS is found responsible for the anti-HBV effect [ 24 ]. TCS has significant and effective dose-dependent and time-dependent inhibition of the expression of HBsAg and HBeAg antigen in HepG2.2.15 cells [ 24 ].…”

Section: Tcs Possesses Multiple Pharmacological Propertiesmentioning

confidence: 99%

“…As the main component in the aqueous extract of Trichosanthis Radix, TCS is found responsible for the anti-HBV effect [ 24 ]. TCS has significant and effective dose-dependent and time-dependent inhibition of the expression of HBsAg and HBeAg antigen in HepG2.2.15 cells [ 24 ]. However, the molecular mechanism of this inhibitory action to HBV is still elusive.…”

Section: Tcs Possesses Multiple Pharmacological Propertiesmentioning

confidence: 99%

“…Recently, it has been found that TCS not only exhibits a very high in vitro antitumor activity to common tumor cells, it can also kill multidrug-resistant cancer cells [ 21 ]. Besides having anti-HIV effect [ 22 ], TCS also exhibits a promising inhibitory effect on Herpes simplex virus (HSV) [ 23 ] and Hepatitis B virus (HBV) [ 24 ]. Moreover, TCS can induce immunosuppression on the non-toxic T-lymphoproliferative responses in humans [ 25 , 26 ], up-regulate interleukin (IL)-4 gene expression and suppress interferon (IFN)-γ gene expression.…”

Section: Introductionmentioning

confidence: 99%

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Structural and Functional Investigation and Pharmacological Mechanism of Trichosanthin, a Type 1 Ribosome-Inactivating Protein

Shi

Wong

Shaw

2018

Toxins

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Trichosanthin (TCS) is an RNA N-glycosidase that depurinates adenine-4324 in the conserved α-sarcin/ricin loop (α-SRL) of rat 28 S ribosomal RNA (rRNA). TCS has only one chain, and is classified as type 1 ribosome-inactivating protein (RIP). Our structural studies revealed that TCS consists of two domains, with five conserved catalytic residues Tyr70, Tyr111, Glu160, Arg163 and Phe192 at the active cleft formed between them. We also found that the structural requirements of TCS to interact with the ribosomal stalk protein P2 C-terminal tail. The structural analyses suggest TCS attacks ribosomes by first binding to the C-terminal domain of ribosomal P protein. TCS exhibits a broad spectrum of biological and pharmacological activities including anti-tumor, anti-virus, and immune regulatory activities. This review summarizes an updated knowledge in the structural and functional studies and the mechanism of its multiple pharmacological effects.

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“…The present study aimed to investigate the resistance of HBV to IFN-α based on a resistant cell model. The HepG2.2.15 cell line is widely used as an in vitro cell model for anti-HBV research (20). Therefore, in the current study, the mechanism of resistance to IFNα-2b and its association with STAT1 was explored using the pre-established IFNα-2b-resistant HepG2.2.15/IFNα-2b cell model (21), so as to provide a basis for finding suitable interventions. )…”

Section: Introductionmentioning

confidence: 99%

Role of STAT1 in the resistance of HBV to IFN‑α

Tang

Wei

2021

Exp Ther Med

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The objective of the present study was to explore the mechanism of hepatitis B virus (HBV) resistance to interferon (IFN), and the role of signal transducer and activator of transcription 1 (STAT1). HepG2.2.15 cells were stimulated with a long-term (6-24 weeks) low-dose interferon (IFN)α-2b (10-70 IU/ml), so as to construct and screen a HepG2.2.15 cell model resistant to IFNα-2b. The changes of STAT1 and other proteins in the JAK-STAT signaling pathway, before and after drug resistance, were compared. The phosphorylation of STAT1 in HepG2.2.15 cells resistant to IFNα-2b was significantly decreased, and the expression level of 2' ,5'-oligoadenylate synthetase 1 was downregulated. Decreased phosphorylation of STAT1 in the JAK-STAT signaling pathway a contributor to the development of resistance to IFN-α in HBV.

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Effect of <I>Radix Trichosanthis</I> and Trichosanthin on Hepatitis B Virus in HepG2.2.15 Cells

Cited by 12 publications

References 0 publications

The anti-cancerous activity of recombinant trichosanthin on prostate cancer cell PC3

The anti-cancerous activity of recombinant trichosanthin on prostate cancer cell PC3

Structural and Functional Investigation and Pharmacological Mechanism of Trichosanthin, a Type 1 Ribosome-Inactivating Protein

Role of STAT1 in the resistance of HBV to IFN‑α

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