Treatment of collagen‐induced arthritis by Natura‐α <i>via</i> regulation of Th‐1/Th‐17 responses

Glatigny, Simon; Blaton, Marie-Agnès; Mencher, Simon K.; Mistou, Sylvie; Lucas, Bruno; Fournier, Catherine; Wang, Long G.; Chiocchia, Gilles

doi:10.1002/eji.200939566

Cited by 12 publications

(5 citation statements)

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“…Natura-alpha has anti-proliferative and anti-inflammatory activities both in vitro and in vivo via inhibition of CDKs and pro-inflammatory cytokines (16, 32). In this study, our data showed that Natura-alpha inhibited growth of prostate cancer cells LNCaP, LNCaP-AI, PC3, and DU145 by MTT and anchorage independent assay.…”

Section: Discussionmentioning

confidence: 99%

Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion

Ligr

McCarron

et al. 2011

Clinical Cancer Research

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Purpose The development of new effective therapeutic agents with minimal side effects for prostate cancer treatment is much needed. Indirubin, an active molecule identified in the traditional Chinese herbal medicine – Qing Dai (Indigo Naturalis), has been used to treat leukemia for decades. However, the anti-cancer properties of Natura-alpha, an indirubin derivative, are not well studied in solid tumors, particularly in prostate cancer. Experimental Design Human prostate cancer cell lines were treated with or without Natura-alpha followed by cell growth and invasion assays measured. The anti-tumor effects of Natura-alpha were examined in nude mice tumor xenograft models, as well as in a patient with advanced hormone refractory metastatic prostate cancer. Signal network proteins targeted by Natura-alpha were analyzed using Proteomic Pathway Array Analysis (PPAA) on xenografts. Results Natura-alpha inhibited the growth of both androgen-dependent (LNCaP), and androgen-independent (LNCaP-AI, PC-3, and DU145) prostate cancer cells with IC50 between 4 to 10 Μm, also inhibits invasion of androgen-independent prostate cancer cells. Its anti-tumor effects were further evident in vivo tumor reduction in androgen-dependent and -independent nude mice tumor xenograft models as well as reduced tumor volume in the patient with hormone refractory metastatic prostate cancer. PPAA revealed that anti-proliferative and anti-invasive activities of Natura-alpha on prostate cancer might primarily be through its down-regulation of Forkhead box M1 (FOXM1) protein. Forced over-expression of FOXM1 largely reversed the inhibition by Natura-alpha. Conclusion Natura-alpha could serve as a novel and effective therapeutic agent for treatment of both hormone sensitive and hormone refractory prostate cancer with minimal side effects.

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Section: Discussionmentioning

confidence: 99%

Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion

Ligr

McCarron

et al. 2011

Clinical Cancer Research

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“…The role of Th17 cells has recently emerged as pivotal in several models of autoimmune and inflammatory diseases (40). Our results suggest that Th17 cells could contribute to both intestinal and joint inflammation in the B27‐transgenic rat model of SpA.…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis‐prone HLA–B27–transgenic rats

Glatigny¹,

Fert²,

Blaton³

et al. 2011

Arthritis & Rheumatism

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Conclusion. Our findings indicate that expanded CD4؉ T cells in B27-transgenic rats exhibit a proinflammatory Th17 phenotype characterized by IL-17A and TNF␣ production. Furthermore, this population is preferentially induced by DCs from B27-transgenic rats. These data point toward an induction of Th17 cells as a possible pathogenic mechanism in this model of SpA. However, their pathogenic role still needs to be shown.

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“…and a clinical score based on disease severity was given for each mouse. Clinical assessment was performed two to three times per week, for up to 60 days in C57/BL6 mice and 35 days in DBA/1 mice as previously described [ 32 ]. Briefly, the date of disease onset was recorded, and the clinical severity of each joint or group of joints (toes, tarsus, ankle, wrist and fingers) was graded as follows: 0 (normal), 1 (swelling or focal redness of finger joints), 2 (mild swelling), 3 (severe swelling) or 4 (necrosis).…”

Section: Methodsmentioning

confidence: 99%

Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models

et al. 2015

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BackgroundGenetic studies have pointed out that CD226 variants, encoding DNAM-1, could be associated with susceptibility to rheumatoid arthritis. Therefore, we aimed to determine the influence of DNAM-1 on the development of arthritis using the collagen-induced arthritis (CIA) mouse model.MethodsCIA was induced in mice on a DBA/1 background, treated in parallel with a DNAM-1 neutralizing monoclonal antibody, a control IgG and PBS, respectively. CIA was also induced in mice deficient for DNAM-1(dnam1−/−) and control dnam-1+/+ mice on a C57/BL6 background. Mice were monitored for clinical and ultrasound signs of arthritis. Histological analysis was performed to search for inflammatory infiltrates and erosions. The Mann–Whitney U test for non-related samples was used for statistical analysis.ResultsThere was a non-significant trend for a less arthritic phenotype in mice receiving anti-DNAM-1 mAb at both clinical, ultrasound and histological assessments. But, we did not observe any difference between dnam1+/+ and dnam1−/− mice for incidence nor severity of clinical arthritis. Histological analysis revealed inflammatory scores similar in both groups, without evidence of erosion. Collagen antibodies levels were similar in all mice, confirming immunization with collagen.ConclusionDespite some clues suggesting a role of DNAM-1 in arthritis, these complementary approaches demonstrate no contribution of CD226/DNAM-1 in the arthritic phenotype. These results contrast with previous studies showing a role in vivo of DNAM-1 in some autoimmune disorders.Electronic supplementary materialThe online version of this article (doi:10.1186/s12950-015-0056-5) contains supplementary material, which is available to authorized users.

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Treatment of collagen‐induced arthritis by Natura‐α via regulation of Th‐1/Th‐17 responses

Cited by 12 publications

References 45 publications

Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion

Natura-Alpha Targets Forkhead Box M1 and Inhibits Androgen-Dependent and -Independent Prostate Cancer Growth and Invasion

Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritis‐prone HLA–B27–transgenic rats

Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models

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