Abstract 4463: Thymoquinone, a potent phytochemical inhibits invasion and cell proliferation in a cell line derived from prostate cancer bone metastasis

The majority of cancer related deaths in the United States result from metastatic malignancies in distant sites such as the brain, lungs, liver and bone. Androgen independent prostate cancer demonstrates a high affinity for metastatic colonization of the bone microenvironment, resulting in skeletal damage that can cause bone pain, hypercalcemia, pathological fracture and spinal cord-compression. Thymoquinone, an extract from the volatile oil of the black seed Nigella sativa has been shown to be a potent phytochemical, traditionally solubilized and administered nasally as an herbal remedy to combat a range of ailments. Thymoquinone functions in the electron transport chain as an electron shuttle, suggesting an anti-oxidant mechanism for its beneficial effects. In addition, thymoquinone exhibits anti-inflammatory and anti-neoplastic effects, inhibiting the growth of pancreatic, colon and prostate cancer cells in-vitro. In order to investigate the effects of thymoquinone on cells that had specifically adapted to growth in bone, we utilized a cell line derived directly from prostate bone metastases. Bone metastases were generated using a recently described ras over-expressing DU145 cell line (Yin et al., 2007). Bone metastases were subsequently isolated, and a cell line termed DU145 Bone 1 was established.

Thymoquinone treatment of DU145 Bone 1 cells resulted in significant dose dependent inhibition of cell proliferation and viability over 24, 48 and 72 hrs. Using an Annexin V/PI assay to investigate the rate of apoptosis, we found that thymoquinone treatment of DU145 Bone 1 cells induced apoptosis in a dose dependent manner. This increase in apoptosis correlated with the decrease in proliferative potential, suggesting that induction of apoptosis may be involved in inhibiting cell proliferation of DU145 Bone 1 cells following thymoquinone treatment. Finally, in an in-vitro transwell assay, thymoquinone treatment (10 to 50 nM) of DU145 Bone 1 cells resulted in near complete inhibition of cell invasion toward fetal calf serum.

In summary, we demonstrate that thymoquinone treatment of a metastatic cell line selected for growth in bone results in significant inhibition of cell proliferation, reduction in cell viability, induction of apoptosis and loss of in-vitro invasive potential. Further in-vivo studies will provide valuable insight into the therapeutic potential of thymoquinone for the treatment of bone metastasis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4463.