Cucurbitacin-B inhibits neuroblastoma cell proliferation through up-regulation of PTEN

Objective: Cucurbitacins belong to a class of highly oxidized tetracyclic triterpenoids. Recent studies suggest that the use of Cucurbitacin could repress Cancer cell progression. However, the biological effect of Cucurbitacin-B in neuroblastoma cells remains unexplored.

Materials and methods: MTT and BrdU (bromodeoxyuridine) incorporation assays were used to determine the anti-proliferation roles of Cucurbitacin-B. Real-Time PCR and Western blot assays were used to detect the expression of cell cycle regulators. Small interfering RNAs (siRNAs) were used to silence the expression of PTEN (Phosphatase and tensin homolog gene).

Results: We found that Cucurbitacin-B inhibited growth and modulated expression of cell-cycle regulators in SHSY5Y cells. At the molecular level, we found that Cucurbitacin-B inhibited Akt signaling activation through up-regulation of PTEN. Indeed, PTEN deficiency using siRNA oligos attenuated the anti-proliferative roles of Cucurbitacin-B.

Conclusions: These results provide evidence for a mechanism that may contribute to the antineoplastic effects of Cucurbitacin-B in neuroblastoma.