A Comprehensive Review on PCSK9 as Mechanistic Target Approach in Cancer Therapy

: PCSK9 is a strongly expressed protein in the liver and brain that binds to the LDLR and regulates cholesterol in the liver effectively. Other receptors with which it interacts include VLDLR, LRP1, ApoER2, and OLR1. PCSK9 gain-of-function results in lysosomal degradation of these receptors, which may result in hyperlipidemia. PCSK9 deficiency results in a lower amount of cholesterol, which reduces cholesterol's accessibility to cancer cells. PCSK9 regulates several proteins and signaling pathways in cancer, including JNK, NF-κВ, and the mitochondrial-mediated apoptotic pathway. In the liver, breast, lungs, and colon tissue, PCSK9 initiates and facilitates cancer development, while in prostate cancer cells, it induces apoptosis. PCSK9 has a significant impact on brain cancer, promoting cancer cell survival by manipulating the mitochondrial apoptotic pathway and exhibiting apoptotic activity in neurons by influencing the NF-κВ, JNK, and caspase-dependent pathways. The PCSK9 impact in cancer at different organs is explored in this study, as well as the targeted signaling mechanisms involved in cancer growth. As a result, these signaling mechanisms may be aimed for the development and exploration of anti-cancer drugs in the immediate future.

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Novel titanocene anti-cancer drugs and their effect on apoptosis and the apoptotic pathway in prostate cancer cells

APOPTOSIS ◽

10.1007/s10495-006-6796-1 ◽

2006 ◽

Vol 11 (7) ◽

pp. 1205-1214 ◽

Cited By ~ 57

Author(s):

K. O'Connor ◽

C. Gill ◽

M. Tacke ◽

F.-J. K. Rehmann ◽

K. Strohfeldt ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Cancer Drugs ◽

Prostate Cancer Cells ◽

Apoptotic Pathway ◽

Anti Cancer

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Activation of the intrinsic-apoptotic pathway in LNCaP prostate cancer cells by genistein- topotecan combination treatments

Functional Foods in Health and Disease ◽

10.31989/ffhd.v3i3.64 ◽

2013 ◽

Vol 3 (3) ◽

pp. 66 ◽

Cited By ~ 2

Author(s):

Vanessa Hörmann ◽

Sivanesan Dhandayuthapani ◽

James Kumi-Diaka ◽

Appu Rathinavelu

Keyword(s):

Prostate Cancer ◽

Cell Death ◽

Cancer Cells ◽

Apoptotic Cell ◽

Treatment Options ◽

Attractive Alternative ◽

Intrinsic Apoptotic Pathway ◽

Prostate Cancer Cells ◽

Apoptotic Pathway ◽

Combination Treatments

Background: Prostate cancer is the second most common cancer in American men. The development of alternative preventative and/or treatment options utilizing a combination of phytochemicals and chemotherapeutic drugs could be an attractive alternative compared to conventional carcinoma treatments. Genistein isoflavone is the primary dietary phytochemical found in soy and has demonstrated anti-tumor activities in LNCaP prostate cancer cells. Topotecan Hydrochloride (Hycamtin) is an FDA-approved chemotherapy for secondary treatment of lung, ovarian and cervical cancers. The purpose of this study was to detail the potential activation of the intrinsic apoptotic pathway in LNCaP prostate cancer cells through genistein-topotecan combination treatments. Methods: LNCaP cells were cultured in complete RPMI medium in a monolayer (70-80% confluency) at 37ºC and 5% CO2. Treatment consisted of single and combination groups of genistein and topotecan for 24 hours. The treated cells were assayed for i) growth inhibition through trypan blue exclusion assay and microphotography, ii) classification of cellular death through acridine/ ethidium bromide fluorescent staining, and iii) activation of the intrinsic apoptotic pathway through Jc-1: mitochondrial membrane potential assay, cytochrome c release and Bcl-2 protein expression.Results: The overall data indicated that genistein-topotecan combination was significantly more efficacious in reducing the prostate carcinoma’s viability compared to the single treatment options. In all treatment groups, cell death occurred primarily through the activation of the intrinsic apoptotic pathway.Conclusion: The combination of topotecan and genistein has the potential to lead to treatment options with equal therapeutic efficiency as traditional chemo- and radiation therapies, but lower cell cytotoxicity and fewer side effects in patients. Key words: topotecan; genistein; intrinsic apoptotic cell death

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Preparation of Catechin Nanoemulsion from Oolong Tea Leaf Waste and Its Inhibition of Prostate Cancer Cells DU-145 and Tumors in Mice

Molecules ◽

10.3390/molecules26113260 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3260

Author(s):

Yu-Hsiang Lin ◽

Chi-Chung Wang ◽

Ying-Hung Lin ◽

Bing-Huei Chen

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Tumor Volume ◽

Tween 80 ◽

Prostate Cancer Cells ◽

Caspase 9 ◽

Oolong Tea ◽

Induced Tumors ◽

Anti Cancer ◽

Tea Leaf

Anti-cancer activity of catechin nanoemulsions prepared from Oolong tea leaf waste was studied on prostate cancer cells DU-145 and DU-145-induced tumors in mice. Catechin nanoemulsions composed of lecithin, Tween-80 and water in an appropriate proportion was prepared with high stability, particle size of 11.3 nm, zeta potential of −67.2 mV and encapsulation efficiency of 83.4%. Catechin nanoemulsions were more effective than extracts in inhibiting DU-145 cell growth, with the IC50 being 13.52 and 214.6 μg/mL, respectively, after 48 h incubation. Furthermore, both catechin nanoemulsions and extracts could raise caspase-8, caspase-9 and caspase-3 activities for DU-145 cell apoptosis, arresting the cell cycle at S and G2/M phases. Compared to control, catechin nanoemulsion at 20 μg/mL and paclitaxel at 10 μg/mL were the most effective in reducing tumor volume by 41.3% and 52.5% and tumor weight by 77.5% and 90.6% in mice, respectively, through a decrease in EGF and VEGF levels in serum.

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Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway

Oncotarget ◽

10.18632/oncotarget.2429 ◽

2014 ◽

Vol 5 (19) ◽

pp. 9335-9348 ◽

Cited By ~ 43

Author(s):

Andressa Ardiani ◽

Sofia R. Gameiro ◽

Anna R. Kwilas ◽

Renee N. Donahue ◽

James W. Hodge

Keyword(s):

Prostate Cancer ◽

Androgen Receptor ◽

T Cell ◽

Cancer Cells ◽

Androgen Deprivation Therapy ◽

Cell Killing ◽

Androgen Deprivation ◽

Prostate Cancer Cells ◽

Apoptotic Pathway

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Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.648985 ◽

2021 ◽

Vol 11 ◽

Author(s):

Zongliang Lu ◽

Wei Song ◽

Yaowen Zhang ◽

Changpeng Wu ◽

Mingxing Zhu ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Castration Resistance ◽

Prostate Cancer Cells ◽

Antitumor Effects ◽

Platycodin D ◽

Downstream Target ◽

Anti Cancer ◽

Pc3 Cells ◽

Androgen Independent

Castration-resistant (androgen-independent) and PTEN-deficient prostate cancer is a challenge in clinical practice. Sorafenib has been recommended for the treatment of this type of cancer, but is associated with several adverse effects. Platycodin D (PD) is a triterpene saponin with demonstrated anti-cancer effects and a good safety profile. Previous studies have indicated that PC3 cells (PTEN -/-, AR -/-) are sensitive to PD, suggesting that it may also be a useful treatment for castration-resistance prostate cancer. We herein investigated the effects of combining PD with sorafenib to treat PTEN-deficient prostate cancer cells. Our data show that PD promotes sorafenib-induced apoptosis and cell cycle arrest in PC3 cells. Of interest, PD only promoted the anti-cancer effects of sorafenib in Akt-positive and PTEN-negative prostate cancer cells. Mechanistic studies revealed that PD promoted p-Akt ubiquitination by increasing the p-Akt level. PD also increased the protein and mRNA expression of FOXO3a, the downstream target of Akt. Meanwhile, PD promoted the activity of FOXO3a and increased the protein expression of Fasl, Bim and TRAIL. Interestingly, when FOXO3a expression was inhibited, the antitumor effects of both PD and sorafenib were individually inhibited, and the more potent effects of the combination treatment were inhibited. Thus, the combination of PD and sorafenib may exert potent anti-cancer effects specifically via FOXO3a. The use of Akt inhibitors or FOXO3a agonists, such as PD, may represent a promising approach for the treatment of androgen-independent and PTEN-deficient prostate cancer.

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Effect of Potassium Iodide Use on Anti-Cancer PDT Applications on PC-3 Prostate Cancer Cells

2019 Medical Technologies Congress (TIPTEKNO) ◽

10.1109/tiptekno.2019.8895107 ◽

2019 ◽

Author(s):

Merve Yunlu ◽

Mustafa Kemal Ruhi ◽

Gunnur Onak ◽

Nermin Topaloglu

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Potassium Iodide ◽

Prostate Cancer Cells ◽

Anti Cancer

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Androgen-Responsive Lncap and Androgen-Independent Du145 Prostate Cancer Cells Display Different Taxol Sensitivities

Microscopy and Microanalysis ◽

10.1017/s1431927600018870 ◽

1999 ◽

Vol 5 (S2) ◽

pp. 1110-1111

Author(s):

Maureen Ripple ◽

Meghan Taylo ◽

Chris Huese ◽

Heide Schatte

Keyword(s):

Prostate Cancer ◽

Cytochrome C ◽

Cancer Cells ◽

Metastatic Breast ◽

Prostate Cancer Cells ◽

Obvious Effect ◽

C Elegans ◽

Transfer Protein ◽

Electron Transfer Protein ◽

Anti Cancer

Taxol has been used as anti-cancer compound against prostate, ovarian, and metastatic breast cancer. While the most obvious effect of taxol is bundeling of microtubules and mitotic arrest, recent studies have demonstrated that taxol is able to induce intranucleosomal DNA fragmentation and typical morphological features of apoptosis in a number of solid tumor cells. These results indicate that taxol may exert its anti-tumor effects via secondary mechanisms which may or may not be related to its primary effects on microtubules. It has been shown that taxol-induced microtubular changes and G2/M arrest are associated with the release of the electron transfer protein cytochrome C from mitochondria into the cytosol. Cytochrome C then binds to APAF-1 (a human homolog of the ced-4 gene of C. elegans), which binds, cleaves, and activates caspase- 9, ultimately resulting in the cleavage and activity of caspase-3. We investigated the effects of taxol (100nM) on microtubules, on DNA, and on the pre-apoptotic mitochondrial events using LNCaP and DU145 prostate cancer cells.

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Calcitriol-Induced Apoptosis in LNCaP Cells Is Blocked By Overexpression of Bcl-21

Endocrinology ◽

10.1210/endo.141.1.7289 ◽

2000 ◽

Vol 141 (1) ◽

pp. 10-17 ◽

Cited By ~ 89

Author(s):

Sarah E. Blutt ◽

Timothy J. McDonnell ◽

Tara C. Polek ◽

Nancy L. Weigel

Keyword(s):

Prostate Cancer ◽

Cell Cycle ◽

Vitamin D ◽

Cancer Cells ◽

Mineral Metabolism ◽

Lncap Cells ◽

Prostate Cancer Cells ◽

Apoptotic Pathway ◽

Induced Apoptosis

Abstract While the role of vitamin D in bone and mineral metabolism has been investigated extensively, the role of the vitamin D receptor in other tissues is less well understood. 1,25-dihydroxyvitamin D3 (calcitriol) can act as a differentiating agent in normal tissues and can inhibit the growth of many cancer cell lines including LNCaP prostate cancer cells. We have shown previously that calcitriol causes LNCaP cell accumulation in the G0/G1 phase of the cell cycle. In this study, we demonstrate that calcitriol also induces apoptosis of LNCaP cells. The calcitriol-induced apoptosis is accompanied by a down-regulation of Bcl-2 and Bcl-XL proteins, both of which protect cells from undergoing apoptosis. Other proteins important in apoptotic control, Bax, Mcl-1, and Bcl-Xs, are unaffected by calcitriol treatment. We find that overexpression of Bcl-2 blocks calcitriol-induced apoptosis and reduces, but does not eliminate, calcitriol-induced growth inhibition. We conclude that both regulation of cell cycle and the apoptotic pathway are involved in calcitriol action in prostate cancer cells.

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