Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

Yao, Jiang; Xie, Jiaxin; Xie, Binbin; Li, Yiran; Jiang, Liming; Sui, Xinbing; Zhou, Xin; Pan, Hongming; Han, Weidong

doi:10.1016/j.bcp.2016.06.004

Cited by 17 publications

(8 citation statements)

References 63 publications

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“…Furthermore, there were some reports that HCQ reduced the expression of TLR4 in several cell types including trophoblastic cells or macrophages. 27,28 According to our data and these previous reports, we suggest that the mechanism of HCQ’s effect on skin and or renal lesions in SLE patients may involve modulation of TLR4 signaling by downregulation of both S100 proteins and TLR4 expression.…”

Section: Discussionsupporting

confidence: 83%

Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus

Wakiya

Kameda

Ueeda

et al. 2019

Lupus

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Objectives We investigated the effect of hydroxychloroquine (HCQ) on S100A8 and S100A9 serum levels in systemic lupus erythematosus (SLE) patients with low disease activity receiving immunosuppressants. Methods SELENA-SLEDAI, Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) and serum levels of complement factors, anti-dsDNA antibodies, and white blood cell, lymphocyte, and platelet counts were used to evaluate disease activity, cutaneous disease activity, and immunological activity, respectively. Serum S100A8 and S100A9 were measured at HCQ administration and after 3 or 6 months using ELISA. Results S100A8 and S100A9 serum levels were elevated at baseline and the magnitude of decrease from baseline at 3 and 6 months after HCQ administration was greater in patients with renal involvement than in those without (baseline: S100A8, p = 0.034; S100A9, p = 0.0084; decrease: S100A8, p = 0.049; S100A9, p = 0.023). S100 modulation was observed in patients with ( n = 17; S100A8, p = 0.0011; S100A9, p = 0.0002) and without renal involvement ( n = 20; S100A8, p = 0.0056; S100A9, p = 0.0012), and was more apparent in patients with improved CLASI activity scores (improved: S100A8, p = 0.013; S100A9, p = 0.0032; unimproved: S100A8, p = 0.055; S100A9, p = 0.055). No associations were observed for immunological biomarkers. Conclusion HCQ may improve organ involvement in SLE by modulating S100 protein levels, especially in patients with renal or skin involvement.

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Section: Discussionsupporting

confidence: 83%

Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus

Wakiya

Kameda

Ueeda

et al. 2019

Lupus

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“…Thus, there is an urgent need to find a compound that has synergistic effects when combined with chemotherapeutic agents to induce an anti-tumor immune response. Of note, HCQ is reported to play a role in the treatment of immune-mediated inflammatory disorders through impacts on the immune system [ 42 ]. In the present study, treatment of the nude mouse model bearing Lewis cells with HCQ/DOX failed to achieve a similar suppression of tumour growth.…”

Section: Discussionmentioning

confidence: 99%

Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages

Yong

Cao

et al. 2018

J Exp Clin Cancer Res

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BackgroundLysosome-associated agents have been implicated as possible chemo-sensitizers and immune regulators for cancer chemotherapy. We investigated the potential roles and mechanisms of hydroxychloroquine (HCQ) in combination with chemotherapy in lung cancer treatment.MethodsThe effects of combined treatment on non-small cell lung cancer (NSCLC) were investigated using cell viability assays and animal models. The influence of HCQ on lysosomal pH was evaluated by lysosomal sensors and confocal microscopy. The effects of HCQ on the tumour immune microenvironment were analysed by flow cytometry.ResultsHCQ elevates the lysosomal pH of cancer cells to inactivate P-gp while increasing drug release from the lysosome into the nucleus. Furthermore, single HCQ therapy inhibits lung cancer by inducing macrophage-modulated anti-tumour CD8+ T cell immunity. Moreover, HCQ could promote the transition of M2 tumour-associated macrophages (TAMs) into M1-like macrophages, leading to CD8+ T cell infiltration into the tumour microenvironment.ConclusionsHCQ exerts anti-NSCLC cells effects by reversing the drug sequestration in lysosomes and enhancing the CD8+ T cell immune response. These findings suggest that HCQ could act as a promising chemo-sensitizer and immune regulator for lung cancer chemotherapy in the clinic.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0938-5) contains supplementary material, which is available to authorized users.

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“…The acute colitis induced by DSS in mice was performed as reported previously. 48 , 49 Briefly, male mice between 8 and 10 weeks old were treated with 2% DSS (molecular weight, 36,000–50,000; MP Biomedicals, Santa Ana, CA) in drinking water for 7 days, followed by regular drinking water for an additional 7 days. Body weight, diarrhea, and bloody stools were recorded daily.…”

Section: Methodsmentioning

confidence: 99%

Intestinal epithelial cell autophagy deficiency suppresses inflammation-associated colon tumorigenesis

Líu

Lou

Liu

et al. 2022

Molecular Therapy - Nucleic Acids

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Therapeutic effect of hydroxychloroquine on colorectal carcinogenesis in experimental murine colitis

Cited by 17 publications

References 63 publications

Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus

Hydroxychloroquine modulates elevated expression of S100 proteins in systemic lupus erythematosus

Hydroxychloroquine induced lung cancer suppression by enhancing chemo-sensitization and promoting the transition of M2-TAMs to M1-like macrophages

Intestinal epithelial cell autophagy deficiency suppresses inflammation-associated colon tumorigenesis

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