scholarly journals Piperine, a Bioactive Component of Pepper Spice Exerts Therapeutic Effects on Androgen Dependent and Androgen Independent Prostate Cancer Cells

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e65889 ◽  
Author(s):  
Abhilash Samykutty ◽  
Aditya Vittal Shetty ◽  
Gajalakshmi Dakshinamoorthy ◽  
Mary Margaret Bartik ◽  
Gary Leon Johnson ◽  
...  
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.


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 ◽  
...  

Oncotarget ◽  
2016 ◽  
Vol 7 (28) ◽  
pp. 44492-44504 ◽  
Author(s):  
Jinhan Xie ◽  
Christina Mølck ◽  
Sophie Paquet-Fifield ◽  
Lisa Butler ◽  
Erica Sloan ◽  
...  

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.


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