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  • Differential regulation of bladder cancer growth by various glucocorticoids: corticosterone and prednisone inhibit cell invasion without promoting cell proliferation or reducing cisplatin cytotoxicity.

Differential regulation of bladder cancer growth by various glucocorticoids: corticosterone and prednisone inhibit cell invasion without promoting cell proliferation or reducing cisplatin cytotoxicity.

Cancer chemotherapy and pharmacology (2014-06-02)
Hitoshi Ishiguro, Takashi Kawahara, Yichun Zheng, Eiji Kashiwagi, Yi Li, Hiroshi Miyamoto
ABSTRACT

A synthetic glucocorticoid, dexamethasone, was recently shown to inhibit bladder cancer cell invasion and metastasis through the glucocorticoid receptor (GR) pathway but increased cell proliferation via inhibiting apoptosis particularly induced by cisplatin. Therefore, comedication with dexamethasone in bladder cancer patients may lead to unfavorable outcomes such as chemoresistance. We here look for any glucocorticoids with inhibitory effects on tumor cell invasion yet inhibitory or at least no stimulatory effects on cell viability. The effects of 10 glucocorticoids on cell viability were first assessed in three bladder cancer lines. Selected compounds were further assessed for their ability in cell viability and apoptosis, with or without cisplatin, as well as in cell invasion. Most of the compounds (hydrocortisone, betamethasone, flumethasone, triamcinolone, budesonide, fluticasone propionate, and fludrocortisone acetate) increased GR-positive cell growth, which was similar to or even stronger than the effect of dexamethasone. Nonetheless, two glucocorticoids (corticosterone, prednisone) showed only marginal effects on cell growth of all the lines tested. They did not significantly reduce the effects of cisplatin on cell proliferation or cisplatin-induced apoptosis. Conversely, corticosterone, prednisone, and dexamethasone similarly inhibited cell invasion and expression of related genes, including MMP-9, VEGF, and IL-6, in GR-positive lines. Corticosterone and prednisone are suggested to have the potential of being harmless, in contrast to dexamethasone, without promoting cell proliferation or inhibiting cytotoxic activity of cisplatin, yet beneficial to bladder cancer patients via suppressing tumor invasion. Our results are thus useful in improving chemotherapy regimens, including optimal glucocorticoids, for urothelial carcinoma.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Hydrocortisone, BioReagent, suitable for cell culture
Sigma-Aldrich
Hydrocortisone, ≥98% (HPLC)
Sigma-Aldrich
Hydrocortisone, γ-irradiated, powder, BioXtra, suitable for cell culture
Sigma-Aldrich
Corticosterone, ≥98.5% (HPLC)
Sigma-Aldrich
Prednisone, ≥98%
Supelco
Hydrocortisone, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Prednisone, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Prednisone, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Corticosterone, ≥92%
Supelco
Budesonide, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Budesonide, ≥99%
Supelco
Betamethasone, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Betamethasone, ≥98%
USP
Hydrocortisone, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Fluticasone propionate, ≥98% (HPLC), powder
Sigma-Aldrich
Hydrocortisone, meets USP testing specifications
Sigma-Aldrich
Triamcinolone
Fluticasone propionate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Fludrocortisone acetate, ≥98%
Hydrocortisone for peak identification, European Pharmacopoeia (EP) Reference Standard
Hydrocortisone, European Pharmacopoeia (EP) Reference Standard
USP
Betamethasone, United States Pharmacopeia (USP) Reference Standard
Betamethasone, European Pharmacopoeia (EP) Reference Standard
Budesonide, European Pharmacopoeia (EP) Reference Standard
Supelco
Corticosterone, VETRANAL®, analytical standard
Supelco
Betamethasone, VETRANAL®, analytical standard
USP
Triamcinolone, United States Pharmacopeia (USP) Reference Standard
Prednisone, European Pharmacopoeia (EP) Reference Standard
Hydrocortisone, British Pharmacopoeia (BP) Assay Standard
Supelco
Hydrocortisone, VETRANAL®, analytical standard