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

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.

scholarly journals Diarylpentanoid (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) (MS13) Exhibits Anti-proliferative, Apoptosis Induction and Anti-migration Properties on Androgen-independent Human Prostate Cancer by Targeting Cell Cycle–Apoptosis and PI3K Signalling Pathways

2021 ◽  
Vol 12 ◽  
Author(s):  
Nurul Azwa Abd Wahab ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Morphological Observation ◽  
Dependent Manner ◽  
Prostate Cancer Cells ◽  
Anti Cancer ◽  
Cancer Activity ◽  
Androgen Independent

Diarylpentanoids exhibit a high degree of anti-cancer activity and stability in vitro over curcumin in prostate cancer cells. Hence, this study aims to investigate the effects of a diarylpentanoid, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (MS13) on cytotoxicity, anti-proliferative, apoptosis-inducing, anti-migration properties, and the underlying molecular mechanisms on treated androgen-independent prostate cancer cells, DU 145 and PC-3. A cell viability assay has shown greater cytotoxicity effects of MS13-treated DU 145 cells (EC50 7.57 ± 0.2 µM) and PC-3 cells (EC50 7.80 ± 0.7 µM) compared to curcumin (EC50: DU 145; 34.25 ± 2.7 µM and PC-3; 27.77 ± 6.4 µM). In addition, MS13 exhibited significant anti-proliferative activity against AIPC cells compared to curcumin in a dose- and time-dependent manner. Morphological observation, increased caspase-3 activity, and reduced Bcl-2 protein levels in these cells indicated that MS13 induces apoptosis in a time- and dose-dependent. Moreover, MS13 effectively inhibited the migration of DU 145 and PC-3 cells. Our results suggest that cell cycle-apoptosis and PI3K pathways were the topmost significant pathways impacted by MS13 activity. Our findings suggest that MS13 may demonstrate the anti-cancer activity by modulating DEGs associated with the cell cycle-apoptosis and PI3K pathways, thus inhibiting cell proliferation and cell migration as well as inducing apoptosis in AIPC cells.

scholarly journals Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Abhilash Samykutty ◽  
Aditya V. Shetty ◽  
Gajalakshmi Dakshinamoorthy ◽  
Ramaswamy Kalyanasundaram ◽  
Gouxing Zheng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Vitamin K2 ◽  
Receptor Expression ◽  
Boyden Chamber ◽  
Therapeutic Effects ◽  
Prostate Cancer Cells ◽  
Mice Model ◽  
Antitumor Effects ◽  
Androgen Independent

In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer potential of VK2 in both androgen-dependent and -independent prostate cancer cells. Our investigations show that VK2 is able to suppress viability of androgen-dependent and androgen-independent prostate cancer cells via caspase-3 and -8 dependent apoptosis. We also show that VK2 treatment reduces androgen receptor expression and PSA secretion in androgen-dependent prostate cancer cells. Our results also implicate VK2 as a potential anti-inflammatory agent, as several inflammatory genes are downregulated in prostate cancer cells following treatment with VK2. Additionally, AKT and NF-kB levels in prostate cancer cells are reduced significantly when treated with VK2. These findings correlated with the results of the Boyden chamber and angiogenesis assay, as VK2 treatment reduced cell migration and angiogenesis potential of prostate cancer cells. Finally, in a nude mice model, VK2 administration resulted in significant inhibition of both androgen-dependent and androgen-independent tumor growth. Overall, our results suggest that VK2 may be a potential therapeutic agent in the treatment of prostate cancer.

scholarly journals Microfluidic Assessment of Drug Effects on Physical Properties of Androgen Sensitive and Non-Sensitive Prostate Cancer Cells

Micromachines ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 532
Author(s):  
Da Luo ◽  
Na Liu ◽  
Yang Chen ◽  
Yan Peng ◽  
Tao Yue ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Physical Properties ◽  
Cancer Cells ◽  
Drug Effects ◽  
Cancer Drug ◽  
Lncap Cells ◽  
Prostate Cancer Cells ◽  
Anti Cancer ◽  
Deformability Cytometry ◽  
Androgen Independent

The identification and treatment of androgen-independent prostate cancer are both challenging and significant. In this work, high-throughput deformability cytometry was employed to assess the effects of two anti-cancer drugs, docetaxel and enzalutamide, on androgen-sensitive prostate cancer cells (LNCaP) and androgen-independent prostate cancer cells (PC-3), respectively. The quantified results show that PC-3 and LNCaP present not only different intrinsic physical properties but also different physical responses to the same anti-cancer drug. PC-3 cells possess greater stiffness and a smaller size than LNCaP cells. As the docetaxel concentration increases, PC-3 cells present an increase in stiffness and size, but LNCaP cells only present an increase in stiffness. As the enzalutamide concentration increases, PC-3 cells present no physical changes but LNCaP cells present changes in both cell size and deformation. These results demonstrated that cellular physical properties quantified by the deformability cytometry are effective indicators for identifying the androgen-independent prostate cancer cells from androgen-sensitive prostate cancer cells and evaluating drug effects on these two types of prostate cancer.

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

Molecules ◽  
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.

scholarly journals Cytostatic Action of Novel Histone Deacetylase Inhibitors in Androgen Receptor-Null Prostate Cancer Cells

2021 ◽  
Vol 14 (2) ◽  
pp. 103
Author(s):  
Zohaib Rana ◽  
Joel D. A. Tyndall ◽  
Muhammad Hanif ◽  
Christian G. Hartinger ◽  
Rhonda J. Rosengren
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Hdac Inhibitors ◽  
G1 Arrest ◽  
Prostate Cancer Cells ◽  
Prostate Tumors ◽  
Normal Prostate ◽  
Pc3 Cells ◽  
Du145 Cells

Androgen receptor (AR)-null prostate tumors have been observed in 11–24% of patients. Histone deacetylases (HDACs) are overexpressed in prostate tumors. Therefore, HDAC inhibitors (Jazz90 and Jazz167) were examined in AR-null prostate cancer cell lines (PC3 and DU145). Both Jazz90 and Jazz167 inhibited the growth of PC3 and DU145 cells. Jazz90 and Jazz167 were more active in PC3 cells and DU145 cells in comparison to normal prostate cells (PNT1A) and showed a 2.45- and 1.30-fold selectivity and higher cytotoxicity toward DU145 cells, respectively. Jazz90 and Jazz167 reduced HDAC activity by ~60% at 50 nM in PC3 lysates. At 4 μM, Jazz90 and Jazz167 increased acetylation in PC3 cells by 6- to 8-fold. Flow cytometry studies on the cell phase distribution demonstrated that Jazz90 causes a G0/G1 arrest in AR-null cells, whereas Jazz167 leads to a G0/G1 arrest in DU145 cells. However, apoptosis only occurred at a maximum of 7% of the total cell population following compound treatments in PC3 and DU145 cells. There was a reduction in cyclin D1 and no significant changes in bcl-2 in DU145 and PC3 cells. Overall, the results showed that Jazz90 and Jazz167 function as cytostatic HDAC inhibitors in AR-null prostate cancer cells.

scholarly journals SHH-N non-canonically sustains androgen receptor activity in androgen-independent prostate cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana Trnski ◽  
Maja Sabol ◽  
Sanja Tomić ◽  
Ivan Štefanac ◽  
Milanka Mrčela ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Cells ◽  
Therapy Resistance ◽  
Androgen Deprivation ◽  
Prostate Cancer Cells ◽  
Androgen Independence ◽  
Androgen Receptor Activity ◽  
Signaling Activation ◽  
Androgen Independent

AbstractProstate cancer is the second most frequent cancer diagnosed in men worldwide. Localized disease can be successfully treated, but advanced cases are more problematic. After initial effectiveness of androgen deprivation therapy, resistance quickly occurs. Therefore, we aimed to investigate the role of Hedgehog-GLI (HH-GLI) signaling in sustaining androgen-independent growth of prostate cancer cells. We found various modes of HH-GLI signaling activation in prostate cancer cells depending on androgen availability. When androgen was not deprived, we found evidence of non-canonical SMO signaling through the SRC kinase. After short-term androgen deprivation canonical HH-GLI signaling was activated, but we found little evidence of canonical HH-GLI signaling activity in androgen-independent prostate cancer cells. We show that in androgen-independent cells the pathway ligand, SHH-N, non-canonically binds to the androgen receptor through its cholesterol modification. Inhibition of this interaction leads to androgen receptor signaling downregulation. This implies that SHH-N activates the androgen receptor and sustains androgen-independence. Targeting this interaction might prove to be a valuable strategy for advanced prostate cancer treatment. Also, other non-canonical aspects of this signaling pathway should be investigated in more detail and considered when developing potential therapies.

A new flavonoid derivative exerts antitumor effects against androgen‐sensitive to cabazitaxel‐resistant prostate cancer cells

The Prostate ◽  
2021 ◽  
Vol 81 (5) ◽  
pp. 295-306
Author(s):  
Renato Naito ◽  
Hiroshi Kano ◽  
Takashi Shimada ◽  
Tomoyuki Makino ◽  
Suguru Kadomoto ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Antitumor Effects
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