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.

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.

Role of 20-Hydroxyeicosatetraenoic Acid (20-HETE) in Androgen-Mediated Cell Viability in Prostate Cancer Cells

2017 ◽  
Vol 8 (4) ◽  
pp. 243-256 ◽  
Author(s):  
Cecilia Colombero ◽  
Daniela Papademetrio ◽  
Paula Sacca ◽  
Eduardo Mormandi ◽  
Elida Alvarez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Hydroxyeicosatetraenoic Acid ◽  
Prostate Cancer Cells

scholarly journals Cisplatin and Paclitaxel Modulated the Cell Survival Potential of Prostate Cancer Cells

Proceedings ◽  
2020 ◽  
Vol 40 (1) ◽  
pp. 42
Author(s):  
Kashani ◽  
Kilbas ◽  
Yerlikaya ◽  
Gurkan ◽  
Arisan
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Cell Viability Assay ◽  
Chemotherapy Drugs

Prostate cancer is the second common cause of death among men worldwide. In the treatment of prostate cancer, conventional chemotherapeutics are commonly used. The plant alkaloid Paclitaxel and platinum-based cisplatin are the most common chemotherapy drugs. The transcription factor p53 has a potential target in the regulation of cell response to DNA damage of prostate cancer. Although the effectiveness of these drugs on prostate cancer cell progression had been proved, the mechanistic action of these drugs on the progression of the disease is not detailed explained. In this study, we aim to examine the function of p53 overexpression in prostate cancer cell survival. Therefore, we treated wild type (wt) and p53 overexpressed PC3 (p53+) prostate cancer cells with cisplatin or paclitaxel. According to the MTT Cell Viability assay, cisplatin (12.5–25–50 µM) was found to be more effective decreasing PC3 and PC3 p53+ cell viability in a dose-dependent manner compared to paclitaxel (12.5–25–50 nM). Colony formation assay showed that treatment of cells with cisplatin or paclitaxel caused the loss of colony forming ability of PC3 and PC3 p53+ cells. In addition, the critical apoptotic markers Caspase-3 and Caspase-9 expressions were altered with cisplatin or paclitaxel treated PC3 wt and p53+ cells.

scholarly journals Molecular Decoy to the Y-Box Binding Protein-1 Suppresses the Growth of Breast and Prostate Cancer Cells whilst Sparing Normal Cell Viability

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12661 ◽  
Author(s):  
Jennifer H. Law ◽  
Yvonne Li ◽  
Karen To ◽  
Michelle Wang ◽  
Arezoo Astanehe ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
Normal Cell ◽  
Binding Protein ◽  
Prostate Cancer Cells ◽  
Breast And Prostate Cancer

Lemongrass (Cymbopogon citratus (D.C.) Stapf) Presents Antitumoral Effect and Improve Chemotherapy Activity in Prostate Cancer Cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Lucas F. Gomes ◽  
Pâmela J.H. Longhi ◽  
Larissa Machado ◽  
Ivana B. Mânica da Cruz ◽  
Marco A.E. Montano ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cell Viability ◽  
Cancer Cells ◽  
Colony Formation ◽  
Antitumor Effect ◽  
Biological Activities ◽  
Prostate Cancer Cells ◽  
Cymbopogon Citratus ◽  
African Green Monkey Kidney

Background: Prostate cancer is the most common visceral neoplasia in men and frequently present chemotherapy resistance. In this context, lemongrass (Cymbopogon citratus (D.C.) Stapf) has been studied, since it presents many important biological activities, such as anticancer. Objective: We investigated the antitumor effect of lemongrass and in chemotherapy activity using prostate cancer cells line (DU-145). Methods: DU-145 cells were exposed to different concentrations of aqueous extract of lemongrass (30; 100; 300; 500 and 1000 μg/mL), isolated and in combination with docetaxel, during 24 and 72 hours. After, cell viability and proliferation, oxidative metabolism, colony formation and cell cycle analyses were performed. Also, we exposed African green monkey kidney cell line (VERO) to the same lemongrass concentrations to investigate a possible toxicity of this extract. Results: Our findings suggested that lemongrass presented an antitumor effect and improved docetaxel chemotherapy activity by decreasing cell viability and proliferation as well as colony formation. Moreover, we found an oxidative stress increased and cell cycle arresting in G0/G1 phase. In addition, this extract presented selectivity action for cancer cells, since it did not cause cytotoxicity in normal cells, ensuring non-toxic therapeutic concentrations. Conclusion: Lemongrass is a promising medicinal plant that could be used during chemotherapeutic treatment, in order to potentiate the antitumor response and decrease the resistance of prostate cancer.

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