Antitumour effects of the angiogenesis inhibitor AGM‐1470 on rat urinary bladder tumours induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine

Osawa, Shuichi; Terashima, Y.; Kimura, Go; Akimoto, Masao

doi:10.1046/j.1464-410x.1999.00911.x

Cited by 12 publications

(2 citation statements)

References 21 publications

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“…However, significant tumor suppression was detected only in the BC31 xenograft model. In the BBN‐induced rat bladder cancer model, the incidence and size of tumors have been reported to be in accordance with concentration, duration and post–duration of BBN intake . The present study set a BBN intake for 10 weeks followed by 20 weeks of luteolin administration.…”

Section: Discussionmentioning

confidence: 84%

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway

et al. 2020

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Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cellcycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3ʹ-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3ʹ-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling. K E Y W O R D Sanimal model, bladder cancer, chemoprevention, mTOR, oxidative stress

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Section: Discussionmentioning

confidence: 84%

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway

et al. 2020

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“…Various preclinical studies evaluated the efficacy for bladder cancer treatment of TNP-470 alone [149][150][151] or in combination with chemotherapeutics [152,153]. In general, they demonstrated the potential of TNP-470 to inhibit tumour growth and a synergistic antitumour effect with gemcitabine [153].…”

Section: Angiogenesismentioning

confidence: 99%

Strategies to improve drug delivery in bladder cancer therapy

Wirth

Plattner

Gabor

2009

Expert Opinion on Drug Delivery

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Bladder cancer is the ninth most common malignancy in the world featuring very high gender variability in occurrence. Current options for bladder cancer therapy include surgery, immunotherapy, chemotherapy and radiotherapy with a trend towards multimodal treatments. However, successful management remains a challenge for urologists and oncologists because of the high risk for recurrence and progression. Particularly in the field of bladder cancer chemotherapy, efficacy of treatment might be improved by advanced drug delivery strategies aimed at prolonged residence time within the bladder cavity and increased permeability of the bladder wall during intravesical instillation. Moreover, a deeper understanding of the biology of bladder carcinogenesis and malignant progression stimulated the development of a new generation of anticancer drugs for targeted therapies that might result in increased treatment specificity together with lower toxic potential and higher therapeutic indices. This review discusses the available strategies for 'targeted therapy', focusing on molecular targets, and for 'controlled delivery', comprising all other approaches towards improved drug delivery.

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TNP-470: The Resurrection of the First Synthetic Angiogenesis Inhibitor

Mann-Steinberg

Satchi‐Fainaro

2008

Angiogenesis

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Antitumour effects of the angiogenesis inhibitor AGM‐1470 on rat urinary bladder tumours induced by N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine

Cited by 12 publications

References 21 publications

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway

Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway

Strategies to improve drug delivery in bladder cancer therapy

TNP-470: The Resurrection of the First Synthetic Angiogenesis Inhibitor

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