Current radiotherapy methods for prostate cancer are associated with undesirable side effects, such as impotence and incontinence. Clearly new approaches for treatment are required. Parthenolide, a major active component of the herbal medicine feverfew, has been shown to have anti-inflammatory and anti-tumour properties in several cancer types. In vitro studies have demonstrated that parthenolide also selectively enhances radiosensitivity of prostate cancer cell lines, but not in primary prostate epithelial cell lines. These specific properties of parthenolide might be utilised to improve current radiotherapy methods. We aimed to study parthenolide’s cytotoxic mechanism in vivo in normal animals and in a prostate tumour model, the TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP), to study changes in radiosensitivity induced by parthenolide treatment. Early tumour development is confined to prostate tissues in the TRAMP model, allowing observation of both tumour and healthy tissues within the same animal.
In pilot studies investigating the effect of parthenolide in normal tissues, male C57BL/6 mice were treated with either 40 mg/kg Parthenolide or 10% ethanol thrice weekly for one week prior to 6 Gy whole body X-irradiation. The TUNEL assay was used to identify apoptosis in situ in tissues 6 hours post-irradiation and apoptosis frequency was determined using CellProfiler software. Parthenolide caused significant protection of normal tissue from high dose radiation induced apoptosis in normal dorsolateral prostate (34.5% reduction, p = 0.002) and spleen (17.3% reduction, p = 0.041) of C57BL/6 mice compared to mice treated with a vehicle control. Further in vivo experiments investigating the effect of parthenolide administered prior to high dose X-irradiation in the TRAMP model identified the same radioprotection from apoptosis in spleen tissue. These results suggest that parthenolide may be a useful radioprotector of normal tissues during radiotherapy. Ongoing studies are aimed at determining if parthenolide also exhibits tumour-specific radiosensitisation of prostate tumour tissue.
This work is supported by a Flinders Medical Centre Foundation “Smiling for Smiddy” PhD scholarship to K.M.