Search

Linalool is an unsaturated terpene that can be found in several plants and exhibits various biological activities. The aim of the present study was to investigate the anticancer activity of linalool using the human prostate cancer 22Rv1 cell line. Flow cytometry was employed to study the effects of linalool on the induction of apoptosis, cell cycle progression, loss of mitochondrial membrane potential and cytochrome c release, whereas the effects of linalool on apoptosis-associated proteins were investigated by western blot analysis. An efficacy study was conducted using 22Rv1 tumor-bearing mice. The expression of the cell proliferation markers Ki-67 and proliferating cell nuclear antigen (PCNA) in xenograft tumors was evaluated by immunohistochemistry. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to study the induction of apoptosis in an in vivo model. Linalool exerted an inhibitory effect on 22Rv1 cell proliferation and induced apoptosis in both in vitro and in vivo models. Western blot analysis indicated that both the mitochondria-mediated intrinsic and death-receptor-mediated extrinsic pathways were involved in the induction of apoptosis. Furthermore, linalool significantly reduced the expression of Ki-67 and PCNA in the 22Rv1 ×enograft model. The findings of the present study provide evidence supporting the anti-proliferative effects of linalool on 22Rv1 human prostate cancer cells, and suggest that linalool may be an effective agent for prostate cancer treatment., (Copyright: © Zhao et al.)

Prostate cancer (PCa) is one of the most common malignancies among men and is the second leading cause of cancer-associated mortality in the developed world. Androgen deprivation therapy (ADT) is the most common treatment for PCa. However, the majority of androgen-sensitive PCa patients will eventually develop resistance to ADT and the disease will become androgen-independent. There is, therefore, an immediate requirement to develop effective therapeutic techniques towards the treatment of recurrent PCa. Oxibendazole (OBZ) is an anthelmintic drug that has also shown promise in the treatment of malignancies. In the present study, the capability of OBZ to repress the growth of PCa cells was assessed in human androgen-independent PCa 22Rv1 and PC-3 cell lines. The growth of the 22Rv1 and PC-3 cell lines, as assessed with a trypan blue exclusion assay, was markedly inhibited by OBZ treatment in vitro , with half-maximal inhibitory concentration values of 0.25 and 0.64 µM, respectively. The mean size of 22Rv1 tumors in nude mice treated with OBZ (25 mg/kg/day) was 47.96% smaller than that of the control mice. Treatment with OBZ increased the expression of microRNA-204 (miR-204), as determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and the level of p53 as determined with western blotting, two well-characterized tumor suppressor genes. When miR-204 expression was knocked down by introduction of an miR-204 inhibitor, the inhibitory effect of OBZ was markedly reduced; however, when it was overexpressed, the inhibitory efficiency of OBZ was markedly higher, indicating that upregulation of miR-204 is key for the efficacy of OBZ. Additionally, OBZ was demonstrated with RT-qPCR to repress the expression of the androgen receptor, and by western blotting to reduce prostate-specific androgen in 22Rv1 cells. The results suggest that OBZ has potential for clinical use in the treatment of recurrent PCa.