Metformin Elicits Antitumor Effects and Downregulates the Histone Methyltransferase Multiple Myeloma SET Domain (MMSET) in Prostate Cancer Cells

The Prostate ◽  
2016 ◽  
Vol 76 (16) ◽  
pp. 1507-1518 ◽  
Author(s):  
Nicole M. A. White-Al Habeeb ◽  
Julia Garcia ◽  
Neil Fleshner ◽  
Bharati Bapat

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


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.



2013 ◽  
Vol 14 (10) ◽  
pp. 5663-5669 ◽  
Author(s):  
Ousman Tamgue ◽  
Cheng-Sen Chai ◽  
Lin Hao ◽  
John-Clotaire Daguia Zambe ◽  
Wei-Wei Huang ◽  
...  


2021 ◽  
Vol 5 (2) ◽  
Author(s):  
◽  
Nalini D ◽  
Ponnulakshmi R ◽  
Monisha Prasad ◽  
Lakshmi Priya ◽  
...  

Background: Prostate cancer is a heterogeneous disease and it is second deadliest malignancy in men and the most commonly diagnosed cancer among men. Current chemo-therapies are limited due to considerable side effects. Recently, many kinds of bioactive phytochemicals have contributed significantly to developing new therapies for chemo-resistant prostate cancer due to their structural diversity. Piperine, a natural alkaloid found in the fruit of black (Piper nigrum Linn) and long (Piper longum Linn), has shown antitumor activities toward various cancer cell lines. However, the antitumor effects of piperine on intrinsic and extrinsic signaling mechanisms in breast cancer has not been elucidated so far. Aim: The study aimed to assess the anticancer activity of piperine in human prostate cancer cells through intrinsic signaling pathways. Methodology: Prostate cancer (PC3) cells were treated with different concentrations of piperine (100 & 200µg/ml) to analyze Bcl-2, p53, case pase-3 and caspase-9 protein expression in PC-3 cells. Cell viability was done using MTT in order to find the optimal dose. Results: MTT assay exhibited that piperine showed cell death at the concentration of 100 and 200µg. It significantly decreased the mRNA and protein expression of anti-apoptotic proteins (Bcl-2 and p-Bcl-2) and increased the levels of p53, casepase-3 and 9 protein expression in both concentrations used. Conclusion: Our present findings show that piperine induces apoptosis in PC-3 cells by inhibition the expression of anti-apoptotic proteins with concomitant increase in the tumor suppressor proteins effectively. Hence, piperine can be considered as a potential phototherapeutic drug for the treatment of prostate cancer which may lead to clinical utility.





2018 ◽  
Vol 38 (11) ◽  
pp. 6069-6083 ◽  
Author(s):  
CHAO WANG ◽  
DAVIT SARGSYAN ◽  
CHENGYUE ZHANG ◽  
RENYI WU ◽  
YUQING YANG ◽  
...  


2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Abhilash Samykutty ◽  
Aditya V. Shetty ◽  
Gajalakshmi Dakshinamoorthy ◽  
Ramaswamy Kalyanasundaram ◽  
Gouxing Zheng ◽  
...  

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.



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