Effect of TDCPP on HeLa cells

What is it about?

Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is one of the most diffused phosphorus flame retardants, highly persistent in the environment and abundant in residential dust samples. To date the cellular targets and mechanisms underlying its toxic effects are not completely understood. The aim of this work was to study the effects of TDCPP on ion transport mechanisms fundamental for the cellular ionic homeostasis, such as Na+-K+-ATPase and Cl- transport. HeLa cells were used as experimental model. TDCPP showed a dose-dependent effect on cell viability in cells exposed for 24h as assessed by MTT test (IC50 = 52.5 µM). The flame retardant was able to exert a dose and time-dependent inhibition on the Na+-K+-ATPase activity. A short-term exposure (1h) was able to exert a significant inhibition at 75 and 100 µM TDCPP, suggesting that the flame retardant is able to directly interfere with the Na+-K+-ATPase phosphate catalytic activity. The sensitivity of the pump to lower TDCPP concentrations increased with the increase of the time of exposure. Following 24h exposure a significant inhibition of about 40 % was evident already at 10 µM and the IC50 value observed was 12.8 ± 6.0 µM. Moreover, TDCPP was also able to impair the NKCC mediated Cl- transport in HeLa cells, as assessed in YFP-H148Q/I152L-expressing HeLa cells. Following 1h exposure TDCPP significantly inhibited the transport by about 30%. The kinetic analysis demonstrated a noncompetitive mechanism of inhibition. In conclusion, results demonstrated the impairment of ion transport mechanisms fundamental for ion homeostasis by TDCPP on HeLa cells.

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Why is it important?

The obtained results disclosed a poor investigated aspect of TDCPP cytotoxicity represented by the interference with the basal mechanisms of cellular ion homeostasis, such as Na+-K+-ATPase and Cl- transport mediated by the NKCC cotransporter. These mechanisms are fundamental for the basal cellular homeostasis and their sensitivity to the flame retardant makes them potential molecular targets underlying the TDCPP cytotoxic effects.