Growth inhibition by Parthenolide in renal cell carcinoma

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Introduction and Objective The sesquiterpene lactone parthenolide, the principal active component in medicinal plants, has been used conventionally to treat migraines or inflammation. Parthenolide is reported to inhibit a common step in NF-κB activation by preventing the TNF-α-induced induction of IκB kinase(IKK) and IKKβ. The objective of this study is to test antitumor effect of parthenolide against renal cell carcinoma( RCC ). Methods Four RCC cell lines( OUR-10, ACHN, Caki-1, NC-65 ) were seeded in 96-well plates and incubated with the parthenolide( 1-10 μM ) for 1-5 days, and assayed for their growth by using MTS assay. Apoptosis was assessed, 0-24 hr after treatment of 2-5 μM parthenolide, by using APOPercentage kit. In vivo xenograft model, 6week-old male nude mice were each given a single subcutaneous injection in the dorsal area of 5×10⁶ OUR-10 cells(n=5, each). Three times a week, mice were each given a subcutaneous injection of parthenolide dissolved in 0.1% ethanol at peritumor site (3μg per body). Control mice were given an injection of 0.1% ethanol. Tumor volumes were measured weekly and determined by the following formula: length × width² × 0.5236. Results The parthenolide showed significant growth inhibition of all RCC cell lines examined in dose-dependent manner, and the percentage of apoptosic cell treated with parthenolide increased dose-dependently. In the xenograft model, the tumors of parthenolide treated group was significantly smaller than those of control group(P < 0.001 ). Conclusions Our results indicate that parthenolide inhibited the growth of RCC cell lines both in vitro and in vivo. Therefore, parthenolide may be a potential antitmor agent against RCC.