scholarly journals Synergistic Effect of Geranylgeranyltransferase Inhibitor, GGTI, and Docetaxel on the Growth of Prostate Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Bin Han ◽  
Naohiro Fujimoto ◽  
Mizuki Kobayashi ◽  
Tetsuro Matsumoto
Keyword(s):  
Prostate Cancer ◽  
Synergistic Effect ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Prostate Cancer Cell ◽  
Inhibitory Effect ◽  
Prostate Cancer Cells ◽  
Growth Inhibitory Effect ◽  
Prostate Cancer Treatment ◽  
Growth Inhibitory

Most advanced prostate cancers progress to castration resistant prostate cancer (CRPC) after a few years of androgen deprivation therapy and the prognosis of patients with CRPC is poor. Although docetaxel and cabazitaxel can prolong the survival of patients with CRPC, inevitable progression appears following those treatments. It is urgently required to identify better or alternative therapeutic strategies. The purpose of this study was to confirm the anti-cancer activity of zoledronic acid (Zol) and determine whether inhibition of geranylgeranylation in the mevalonate pathway could be a molecular target of prostate cancer treatment. We examined the growth inhibitory effect of Zol in prostate cancer cells (LNCaP, PC3, DU145) and investigated a role of geranylgeranylation in the anticancer activity of Zol. We, then, evaluated the growth inhibitory effect of geranylgeranyltransferase inhibitor (GGTI), and analyzed the synergy of GGTI and docetaxel by combination index and isobolographic analysis. Zol inhibited the growth of all prostate cancer cell lines tested in a dose-dependent manner through inhibition of geranylgeranylation. GGTI also inhibited the prostate cancer cell growth and the growth inhibitory effect was augmented by a combination with docetaxel. Synergism between GGTI and docetaxel was observed across a broad range of concentrations. In conclusion, our results demonstrated that GGTI can inhibit the growth of prostate cancer cells and has synergistic effect with docetaxel, suggesting its potential role in prostate cancer treatment.

Novel nitrogen containing steroid derivatives for prostate cancer treatment

2021 ◽  
Vol 28 ◽  
Author(s):  
Alexandra S. Latysheva ◽  
Vladimir A. Zolottsev ◽  
Vadim S. Pokrovsky ◽  
Irina I. Khan ◽  
Alexander Yu. Misharin
Keyword(s):  
Prostate Cancer ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Significant Activity ◽  
Prostate Cancer Cells ◽  
Prostate Cancer Treatment ◽  
Derivatives Of

: This mini review focuses on the investigation of novel nitrogen containing steroid derivatives potentially applicable for prostate cancer treatment. It covers last decade of literature with highlights on the structure of new steroid compounds exhibiting significant activity in prostate cancer cells and possessing pharmacological potency. New derivatives of known anti-prostate cancer agents: abiraterone and galeterone, new derivatives of androstane and pregnane modified with nitrogen containing heterocycles, and some related steroid derived compounds are discussed in the review.

A key regulator of cholesterol homoeostasis, SREBP-2, can be targeted in prostate cancer cells with natural products

2012 ◽  
Vol 446 (2) ◽  
pp. 191-201 ◽  
Author(s):  
James R. Krycer ◽  
Lisa Phan ◽  
Andrew J. Brown
Keyword(s):  
Prostate Cancer ◽  
Natural Products ◽  
Cell Viability ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Tree Bark ◽  
Prostate Cancer Cells ◽  
Prostate Cancer Treatment ◽  
Cholesterol Levels ◽  
Birch Tree

There is growing evidence showing that prostate cancer cells have perturbed cholesterol homoeostasis, accumulating cholesterol to promote cell growth. Consequently, cholesterol-lowering drugs such as statins are being evaluated in prostate cancer treatment. Furthermore, natural products such as betulin (from birch tree bark) and tocotrienol (a minor form of vitamin E) have been shown to lower cholesterol levels. Using these drugs and oxysterols, we have determined which aspects of cholesterol homoeostasis should be targeted in prostate cancer, e.g. cellular cholesterol levels are increased by the transcription factor SREBP-2 (sterol-regulatory-element-binding protein isoform 2), whereas LXR (liver X receptor) promotes cholesterol efflux. Whereas betulin exerted non-specific effects on cell viability, tocotrienols produced a strong direct correlation between SREBP-2 activity and cell viability. Mechanistically, tocotrienols lowered SREBP-2 activity by degrading mature SREBP-2 independently of the proteasome. In contrast, no correlation was seen between LXR activity and cell viability, implying that SREBP-2 is a better target than LXR for prostate cancer treatment. Lastly, androgen-dependent and -independent LNCaP cells were both sensitive to tocotrienols. Overall, this suggests that tocotrienols and other drugs targeting the SREBP-2 pathway are a potential therapeutic option for prostate cancer.

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