Prostate Cancer Abstracts 6 - Curcumin

© 2011

Prostate cancer and curcumin: add spice to your life

            (Aggarwal 2008) Download

Possible benefits of curcumin regimen in combination with taxane chemotherapy for hormone-refractory prostate cancer treatment

            (Cabrespine-Faugeras, Bayet-Robert et al. 2010) Download

Complementary and alternative therapies for neoplastic diseases treatment and prevention receive increasing attention from the medical community. Prostate cancer (PC) is the most frequently diagnosed malignancy and the second major cause of male death in industrialized countries. The chemopreventive properties and clinical safety of curcumin, a polyphenolic derivative, have already been established. However, curcumin regimen value in addition to conventional hormone refractory (HR) PC treatment remains largely unknown. This review article summarizes mechanisms by which curcumin may decrease HRPC aggressive proliferation and potentiate activity of taxane therapy. Our analysis suggests that curcumin alone has a therapeutic value in HRPC. In combination with a taxane agent, this compound may enhance cytotoxicity and retard PC cell resistance to taxane. As a consequence, a rationale is provided for considering the possible benefits of curcumin regimen in combination with taxane therapy in HRPC patients.

Curcumin interrupts the interaction between the androgen receptor and Wnt/beta-catenin signaling pathway in LNCaP prostate cancer cells

            (Choi, Lim et al. 2010) Download

Recently, studies have investigated the significance of the Wnt/beta-catenin pathway in prostate cancer. The transcriptional activity of the androgen receptor (AR) is modulated by interaction with coregulators, one of which is beta-catenin. Curcumin, a dietary yellow pigment of Curcuma longa, has emerged as having a chemopreventive role. Although curcumin has been shown to inhibit AR expression, its molecular mechanism has not been fully elucidated. In this study, whether curcumin mediates the Wnt/beta-catenin signaling pathway with regard to AR/beta-catenin interactions was studied. Curcumin was shown to induce significant inhibition of AR expression in a dose-dependent manner. Marked curcumin-induced suppression of beta-catenin was shown in the nuclear and cytoplasmic extracts as well as whole cell lysates. Further analysis revealed that phosphorylation of Akt and glycogen synthase kinase-3beta were attenuated, but phosphorylated beta-catenin was increased after curcumin treatment. Finally, cyclin D1 and c-myc, the target gene of the beta-catenin/T-cell factor transcriptional complex, were also decreased. These findings suggest that curcumin modulates the Wnt/beta-catenin signaling pathway and might have a significant role in mediating inhibitory effects on LNCaP prostate cancer cells.

Curry spice curcumin and prostate cancer

            (Kurien and Scofield 2009) Download

Antitumor activity of natural compounds, curcumin and PKF118-310, as Wnt/beta-catenin antagonists against human osteosarcoma cells

            (Leow, Tian et al. 2010) Download

Aberrant activation of the Wnt/beta-catenin signaling pathway promotes osteosarcoma tumorigenesis and metastasis. In this study, we tested the hypothesis that osteosarcoma progression may be delayed by disrupting the Wnt/beta-catenin pathway using small molecule inhibitors such as curcumin and PKF118-310. Effective inhibitions of the Wnt/beta-catenin pathway by curcumin and PKF118-310 in osteosarcoma cells were shown by the suppression of both intrinsic and activated beta-catenin/Tcf transcriptional activities using luciferase reporter assays. Western blot analysis revealed that there was no change in the amount of cytosolic beta-catenin, although nuclear beta-catenin was markedly reduced by treatment with either compounds. We next performed wound healing and Matrigel invasion assays and observed a dose-dependent decrease in osteosarcoma cell migration and invasion with curcumin and PKF118-310 treatment. Overexpression of the wild-type beta-catenin plasmid in osteosarcoma cells resulted in enhanced cell invasiveness but this effect was significantly overcome by curcumin. Gelatin zymography and Western blotting showed that reduced cell invasion with curcumin and PKF118-310 treatment correlated with the activity and protein level of matrix metalloproteinase-9 under conditions of intrinsic or extrinsic Wnt/beta-catenin activation. Using cell apoptosis assay and cell cycle analysis, we further showed that the anti-proliferative effect of PKF118-310 is attributed to PKF118-310-induced apoptosis and G2/M phase arrest. Lastly, we observed that these anti-cancer effects correlated with the decreased expression of cyclin D1, c-Myc and survivin. Our findings strongly suggest that curcumin and PKF118-310 have great therapeutic potential for the treatment of osteosarcoma.


An evaluation of the anti-neoplastic activity of curcumin in prostate cancer cell lines

            (Piantino, Salvadori et al. 2009) Download

OBJECTIVE: The aim of our study is to investigate the anti-neoplastic effect of curcumin in prostate cancer cell lines. Specifically, we are using the LNCaP cell line and another prostate cell line developed in our laboratory, PcBra1. The PcBra1 cells were derived from a localized, obstructive prostate cancer with a Gleason score of 9 (4+5). MATERIALS AND METHODS: A prostate cancer cell line was isolated from a localized, obstructive prostate cancer with a Gleason score of 9 (4+5), and it was characterized using immunohistochemistry. After six passages, the new cell line was treated with varying doses of curcumin: 10 microM, 25 microM or 50 microM. Apoptosis was detected by flow cytometry using Annexin V FITC. For comparison, the same experiment was performed using the well-established metastatic prostate cancer cell line, LNCaP. RESULTS: Increasing concentrations of curcumin promoted more apoptosis in the PcBra1 cells. Exposure to 10 and 25 microM curcumin induced apoptosis in 31.9% and 52.2% of cells, respectively. Late apoptosis was induced in 37% of cells after treatment with 10 microM curcumin and 35% of cells with a 25 microM treatment. Necrosis accounted for less than 10% of the death in these cells at those two concentrations. When curcumin was used at 50 microM, apoptosis was observed in 64.3% of the cells. Including late apoptosis and necrosis, 98.6% of the cells died in response to 50 microM curcumin. Results with the LNCaP cells were similar although late apoptosis was the main phenomenon at 25 microM. CONCLUSION: We have shown that curcumin acts on localized prostate cancer to induce apoptosis and may therefore be an option as a future therapeutic agent.

Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway

            (Teiten, Gaascht et al. 2011) Download

Activation of the Wingless (Wnt)/ss-catenin signaling pathway contributes to prostate tumorigenesis and metastasis. Depending of the stage of prostate cancer development, current drug therapies are of limited efficiency, so that prevention with natural compounds appears as an attractive strategy especially due to the slow progressive development of prostate cancer. We report here that the chemopreventive agent curcumin from the rhizome of Curcuma longa was able to affect cell proliferation of androgen-dependent prostate cancer through the induction of cell cycle arrest in G2 and modulation of Wnt signaling. Curcumin decreases the level of Tcf-4, CBP and p300 proteins implicated in the Wnt transcriptional complex that leads to the decrease of ss-catenin/Tcf-4 transcriptional activity and of the expression of ss-catenin target genes (cyclin D1 and c-myc). Subsequent cell death induction is linked to autophagy. Interestingly, in androgen-independent prostate cancer cells, curcumin does not affect Wnt/ss-catenin transcriptional activity. Altogether our results suggest that curcumin is an interesting chemopreventive agent for early stage prostate cancer.

Chemopreventive potential of curcumin in prostate cancer

            (Teiten, Gaascht et al. 2010) Download

The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention in order to prevent or eradicate prostate malignancies. We present here an overview of the chemopreventive potential of curcumin (diferuloylmethane), a well-known natural compound that exhibits therapeutic promise for prostate cancer. In fact, it interferes with prostate cancer proliferation and metastasis development through the down-regulation of androgen receptor and epidermal growth factor receptor, but also through the induction of cell cycle arrest. It regulates the inflammatory response through the inhibition of pro-inflammatory mediators and the NF-kappaB signaling pathway. These results are consistent with this compound's ability to up-induce pro-apoptotic proteins and to down-regulate the anti-apoptotic counterparts. Alone or in combination with TRAIL-mediated immunotherapy or radiotherapy, curcumin is also reported to be a good inducer of prostate cancer cell death by apoptosis. Curcumin appears thus as a non-toxic alternative for prostate cancer prevention, treatment or co-treatment.


References

Aggarwal, B. B. (2008). "Prostate cancer and curcumin: add spice to your life." Cancer Biol Ther 7(9): 1436-40.

Cabrespine-Faugeras, A., M. Bayet-Robert, et al. (2010). "Possible benefits of curcumin regimen in combination with taxane chemotherapy for hormone-refractory prostate cancer treatment." Nutr Cancer 62(2): 148-53.

Choi, H. Y., J. E. Lim, et al. (2010). "Curcumin interrupts the interaction between the androgen receptor and Wnt/beta-catenin signaling pathway in LNCaP prostate cancer cells." Prostate Cancer Prostatic Dis 13(4): 343-9.

Kurien, B. T. and R. H. Scofield (2009). "Curry spice curcumin and prostate cancer." Mol Nutr Food Res 53(7): 939-40.

Leow, P. C., Q. Tian, et al. (2010). "Antitumor activity of natural compounds, curcumin and PKF118-310, as Wnt/beta-catenin antagonists against human osteosarcoma cells." Invest New Drugs 28(6): 766-82.

Piantino, C. B., F. A. Salvadori, et al. (2009). "An evaluation of the anti-neoplastic activity of curcumin in prostate cancer cell lines." Int Braz J Urol 35(3): 354-60; discussion 361.

Teiten, M. H., F. Gaascht, et al. (2011). "Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway." Int J Oncol 38(3): 603-11.

Teiten, M. H., F. Gaascht, et al. (2010). "Chemopreventive potential of curcumin in prostate cancer." Genes Nutr 5(1): 61-74.