Effects of cisplatin on human thyrocytes in monolayer or follicle culture

Abstract

Cis-diamminedichloroplatinum (II) (cisplatin) is a widely used anticancer drug which induces many side-effects, but its action on the thyroid gland is still unknown. We have investigated the effects of this drug on human thyrocytes cultured in monolayers or in follicles and stimulated with 200 microU TSH/ml. After 72 h in culture, different concentrations of cisplatin (15, 30 and 75 microM) caused partial or total inhibition of cyclic AMP (cAMP), thyroglobulin (Tg) and tri-iodothyronine (T3) production, whereas thyroxine levels increased in the medium of thyrocytes cultured as follicles. Small doses of the drug did not affect thyrocyte production. Decreases in neutral-red uptake by thyroid cells and in intracellular lactate dehydrogenase, alpha-hydroxybutyryldehydrogenase and creatine phosphokinase activities were induced by 30 and 75 microM cisplatin. These data show that high concentrations of cisplatin had a cytotoxic effect on thyrocytes. Cisplatin also induced inhibition of the production of cAMP, Tg and T3.

Thyroid Dysfunction as an Unintended Side Effect of Anticancer Drugs

“…However, few studies prospectively evaluated thyroid dysfunction induced by cytotoxic agents in adult populations. Lomustine, vincristine, and cisplatin have shown in vitro effects on thyroid cells (10). In small series, 5-fluorouracil and L-asparaginase alter levels of thyroid hormone-binding proteins without clinical consequence (11)(12)(13)(14)(15)(16).…”

Thyroid cell survival in coculture with autologous peripheral or intrathyroidal lymphocytes

“…The intracellular LDH activity was immediately determined as previously described (Massart et al, 1992).…”

In vitro modulation of cisplatin accumulation in human ovarian carcinoma cells by pharmacologic alteration of microtubules.

“…On the other hand, DDP accumulation can be modulated by a variety ofdifferent agents indicating that DDP transport is more complex than simple passive diffusion (1). Several recent reports have described a link between DDP and the cAMP signal transduction pathway (3,4). On one hand, DDP has been shown to inhibit the production of cAMP in human thyrocytes (3).…”

“…Several recent reports have described a link between DDP and the cAMP signal transduction pathway (3,4). On one hand, DDP has been shown to inhibit the production of cAMP in human thyrocytes (3). On the other hand, forskolin, an adenyl cyclase agonist, and 3-isobutyl-l-methylxanthine (IBMX), a phosphodiesterase inhibitor, caused 2.1-and 2.3-fold increases, respectively, in the short-term accumulation of DDP relative to untreated cells (4).…”