The Xc− inhibitor sulfasalazine improves the anti-cancer effect of pharmacological vitamin C in prostate cancer cells via a glutathione-dependent mechanism

2019 ◽  
Vol 43 (1) ◽  
pp. 95-106 ◽  
Author(s):  
Zijie Zheng ◽  
Ganhua Luo ◽  
Xinchong Shi ◽  
Yali Long ◽  
Wanqing Shen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin C ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Anti Cancer ◽  
Dependent Mechanism

scholarly journals Pharmacological Vitamin C Treatment Impedes the Growth of Endogenous Glutamine-Dependent Cancers by Targeting Glutamine Synthetase

2021 ◽  
Vol 12 ◽  
Author(s):  
Yali Long ◽  
Jia Qiu ◽  
Bing Zhang ◽  
Peng He ◽  
Xinchong Shi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Glutamine Synthetase ◽  
Vitamin C ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Therapeutic Effect ◽  
Critical Role ◽  
Prostate Cancer Cells ◽  
Anti Cancer

Purpose: Glutamine synthetase (GS) is the only currently known enzyme responsible for synthesizing endogenous glutamine (Gln). GS exerts a critical role in the oncogenesis of endogenous Gln-dependent cancers, making it an attractive target for anti-tumor therapies. A mixed-function oxidation system consisting of vitamin C (VC), oxygen, and trace metals can oxidize GS and promote its degradation. The current study aims to explore the effect of pharmacological VC treatment on GS.Methods: Endogenous Gln-dependent cancer lines (breast cancer MCF7 and prostate cancer PC3) were selected to establish chronic Gln-deprived MCF7 and PC3 cell models. The expression of GS in parental and chronic Gln-deprived tumor cells exposed to VC treatment and control was determined by Western blot analysis. The anti-cancer effects of VC on parental and chronic Gln-deprived tumor cells were assessed by CCK-8 and annexin V-FITC/PI FACS assays. In addition, changes in cellular reactive oxygen species (ROS), glutathione (GSH) levels and NADPH/NADP + ratio were analyzed to explore the underlying mechanisms. Moreover, BALB/c nude mice xenografting with parental and chronic Gln-deprived prostate cancer cells were constructed to evaluate the in vivo therapeutic effect of VC. Finally, tumor 13N-ammonia uptake in mice bearing prostate cancer xenografts was analyzed following treatment with VC and the expression of GS in xenografts were detected by immunohistochemistry.Results: Cells overexpressing GS were obtained by chronic Gln deprivation. We found that the cytotoxic effect of VC on cancer cells was positively correlated with the expression of GS. Additionally, VC treatment led to a significant increase in ROS production, as well as GSH depletion and NADPH/NADP + reduction. These changes could be reversed by the antioxidant N-acetyl-L-cysteine (NAC). Furthermore, pharmacological VC treatment exhibited a more significant therapeutic effect on xenografts of prostate cancer cells overexpressing GS, that could be well monitored by 13N-ammonia PET/CT imaging.Conclusion: Our findings indicate that VC can kill cancer cells by targeting glutamine synthetase to induce oxidative stress. VC could be used as an anti-cancer treatment for endogenous glutamine-dependent cancers.

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 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.

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

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.

A histone deacetylation-dependent mechanism for transcriptional repression of the gap junction gene cx43 in prostate cancer cells

The Prostate ◽  
2006 ◽  
Vol 66 (11) ◽  
pp. 1151-1161 ◽  
Author(s):  
Maite Hernandez ◽  
Qing Shao ◽  
Xiang-Jiao Yang ◽  
Shi-Ping Luh ◽  
Mustapha Kandouz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gap Junction ◽  
Cancer Cells ◽  
Transcriptional Repression ◽  
Histone Deacetylation ◽  
Prostate Cancer Cells ◽  
Dependent Mechanism

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

APOPTOSIS ◽  
2006 ◽  
Vol 11 (7) ◽  
pp. 1205-1214 ◽  
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

Attenuation of nucleoside and anti-cancer nucleoside analog drug uptake in prostate cancer cells by Cimicifuga racemosa extract BNO-1055

Phytomedicine ◽  
2013 ◽  
Vol 20 (14) ◽  
pp. 1306-1314 ◽  
Author(s):  
Andrea Dueregger ◽  
Fabian Guggenberger ◽  
Jan Barthelmes ◽  
Günther Stecher ◽  
Markus Schuh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Nucleoside Analog ◽  
Drug Uptake ◽  
Prostate Cancer Cells ◽  
Cimicifuga Racemosa ◽  
Anti Cancer
Sign in / Sign up

Export Citation Format

Share Document