scholarly journals Afzelin exhibits anti-cancer activity against androgen-sensitive LNCaP and androgen-independent PC-3 prostate cancer cells through the inhibition of LIM domain kinase 1

2015 ◽  
Vol 10 (4) ◽  
pp. 2359-2365 ◽  
Author(s):  
KAI-CHANG ZHU ◽  
JIAN-MEI SUN ◽  
JIAN-GUO SHEN ◽  
JI-ZHONG JIN ◽  
FENG LIU ◽  
...  
2021 ◽  
Vol 12 ◽  
Author(s):  
Nurul Azwa Abd Wahab ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Zongliang Lu ◽  
Wei Song ◽  
Yaowen Zhang ◽  
Changpeng Wu ◽  
Mingxing Zhu ◽  
...  

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.


2009 ◽  
Vol 286 (2) ◽  
pp. 161-171 ◽  
Author(s):  
Huei-Mei Chen ◽  
Yang-Chang Wu ◽  
Yi-Chen Chia ◽  
Fang-Rong Chang ◽  
Hseng-Kuang Hsu ◽  
...  

Micromachines ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 532
Author(s):  
Da Luo ◽  
Na Liu ◽  
Yang Chen ◽  
Yan Peng ◽  
Tao Yue ◽  
...  

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.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3260
Author(s):  
Yu-Hsiang Lin ◽  
Chi-Chung Wang ◽  
Ying-Hung Lin ◽  
Bing-Huei Chen

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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Diana Trnski ◽  
Maja Sabol ◽  
Sanja Tomić ◽  
Ivan Štefanac ◽  
Milanka Mrčela ◽  
...  

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.


PLoS ONE ◽  
2009 ◽  
Vol 4 (9) ◽  
pp. e7068 ◽  
Author(s):  
Maria Katsogiannou ◽  
Charbel El Boustany ◽  
Florian Gackiere ◽  
Philippe Delcourt ◽  
Anne Athias ◽  
...  

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