scholarly journals Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Hyo-Jeong Lee ◽  
Deok-Beom Jung ◽  
Eun Jung Sohn ◽  
Hanna Hyun Kim ◽  
Moon Nyeo Park ◽  
...  

Although cryptotanshinone (CT) was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1αin CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1αaccumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1αsiRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1αduring hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1αto VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

1998 ◽  
Vol 31 (5) ◽  
pp. 435-445 ◽  
Author(s):  
Tetsuo Takagi ◽  
Susumu Takekoshi ◽  
Takeshi Okabe ◽  
Hidetaka Nagata ◽  
Takao Honma ◽  
...  

2012 ◽  
Vol 109 (2) ◽  
pp. 210-222 ◽  
Author(s):  
So Young Park ◽  
Chu Won Nho ◽  
Dae Young Kwon ◽  
Young-Hee Kang ◽  
Ki Won Lee ◽  
...  

Maslinic acid is found in various natural sources, most notably in pomace olive oil, and exerts pro-apoptotic activities in various cancer cells in vitro. In the present study, DU145 human prostate cancer cells were cultured with 0–25 μm-maslinic acid to examine the effects of maslinic acid on the metastatic capacity of prostate cancer cells. Maslinic acid significantly (P <0·05) inhibited the basal and epidermal growth factor (EGF)-induced migration (27–64 %), invasion (23–60 %) and adhesion (8–40 %) of DU145 cells. Maslinic acid significantly (P <0·05) down-regulated both basal and EGF-stimulated secretion of matrix metalloproteinase (MMP)-9 (25–67 %), MMP-2 (50–86 %), urokinase-type plasminogen activator (uPA, about 100 %), vascular endothelial growth factor (VEGF, 98–100 %) and tissue inhibitors of metalloproteinases (TIMP)-1, as well as expression of uPA receptor (uPAR), intercellular adhesion molecules (22–33 %), vascular cell adhesion molecules (23–46 %) and E-cadherin, whereas it increased TIMP-2 secretion. Maslinic acid dramatically reduced the levels of hypoxia-inducible factor-1α (HIF-1α) protein and mRNA; the reduction was accompanied by reduced stability, nuclear levels and transcriptional activity of HIF-1α. The levels of phospho-Akt and phospho-extracellular signal-related kinase (ERK) were reduced in cells treated with maslinic acid, and the phosphoinositide 3-kinase inhibitor LY294002 and the mitogen-activated protein kinase kinase inhibitor PD98059 reduced HIF-1α levels and VEGF secretion. The results show that maslinic acid markedly inhibited the migration, invasion and adhesion of DU145 prostate cancer cells. Suppressing HIF-1α activation by inhibiting Akt and ERK activation may be part of the mechanism by which maslinic acid inhibited uPAR, E-cadherin, VEGF and MMP expression in DU145 cells.


The Prostate ◽  
2006 ◽  
Vol 66 (4) ◽  
pp. 430-438 ◽  
Author(s):  
Fuminori Teraishi ◽  
Shuhong Wu ◽  
Satoshi Inoue ◽  
Lidong Zhang ◽  
John J. Davis ◽  
...  

2013 ◽  
Vol 31 (8) ◽  
pp. 1448-1456 ◽  
Author(s):  
Chang Wook Jeong ◽  
Cheol Yong Yoon ◽  
Seong Jin Jeong ◽  
Sung Kyu Hong ◽  
Seok-Soo Byun ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e38000 ◽  
Author(s):  
Yong-Qing Liu ◽  
Xiao-Yan Hu ◽  
Tao Lu ◽  
Yan-Na Cheng ◽  
Charles Y. F. Young ◽  
...  

2019 ◽  
Vol 13 (5) ◽  
pp. 331-337
Author(s):  
S. A. Demchenko ◽  
Yu. A. Fedchenkova ◽  
T. А. Bukhtiarova ◽  
L. S. Bobkova ◽  
V. V. Sukhoveev ◽  
...  

Pharmacotherapy of prostate cancer is an important part in combating oncologic diseases. This is very relevant, because prostate cancer is a cause of 10 % of deaths from all cancerous diseases in males. The aim of the study – to synthesize novel derivatives of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid arylamides and to evaluate their antitumor activity against PC-3 prostate cancer cells. By reaction of equimolar amounts of 2-methoxy-3,4,5,6-tetrahydro-7H-azepine with a-amino-4-chloroacetophenone chlorohydrate, 3-(4-chlorophenyl)-6,7,8,9- tetrahydro-5Н-imidazo[1,2-a]azepine was synthesized. By alkylation of a-bromo-4-іsopropylacetophenone in ethylacetate and following treatment of the obtained intermediary quaternary salt with excess of 5 % NaOH solution,1-(41-isopropylphenyl)-4-(42chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd] azulene was synthesized. By boiling it with equimolar amounts of correspondding arylisocyanates in dried benzol, an array of 1-(41-iso propylphenyl)-4(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid arylamides were synthesized. Structure and purity of all compounds obtained were confirmed by data of MR1Н spectroscopy. Lipophilicity (LogP) of compounds 6 and 8 a-i was calculated with the ACD LogP program. Antitumor activity of 1-(41-isopropylphenyl)-4-(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd]azulene-2-carboxylic acid (3-methylphenyl) and (3-methoxyphenyl)-amides was evaluated at in vitro test on prostate cancer PC-3 cell lines. It is indicated, that at concentration of 10–5 M these compounds exceed 5-fluorouracil as comparison drug in inhibiting PC-3 prostate cancer cells growth by 52.32 % and 3.93 % correspondingly. The data obtained substantiate feasibility of further studies of 1-(41-isopro pylphenyl)-4-(42-chlorophenyl)-5,6,7,8-tetrahydro-2,4а-diazacyclopenta[cd] azulene-2-carboxylic acid arylamides as new, potential antitumor medicines for prostate cancer treatment.


2019 ◽  
Author(s):  
Sila Appak-Baskoy ◽  
lknur Kulcanay Sahin ◽  
Ozgun Teksoy ◽  
Mustafa Cengiz ◽  
Asuman Deveci Ozkan ◽  
...  

AbstractTreatment options to improve overall survival rate of prostate cancer patients are limited since tumor cells acquire resistance to the chemotherapeutic drugs. We aimed to determine anticancer effects of stone alkaline water (SAW) on PC-3 and DU-145 prostate adenocarcinoma cell lines. SAW was obtained by triturating high stones under vacuum at 3000 °C. High mineral and trace element containing fraction of SAW was used for the experiments. Viability of the tumor cells was analyzed using tetrazolium based WST-1 cell proliferation assay, cell cycle analysis was carried out with Propidum Iodide staining (Muse™ Cell Cycle Kit). Acridine Orange and Annexin V stainings were done to analyze the cellular morphology and to determine apoptosis. Tumor cell derived angiogenesis was analyzed with migration and tube formation assays. SAW treatment resulted in accumulation of cells at G0/G1 phase and inhibited tumor cell induced HUVEC tube formation and migration. SAW treatment significantly decreased viability of PC-3 and DU-145 prostate adenocarcinoma cells and induced apoptotic cell death. Intriguingly, treatment of the prostate cancer cells with SAW inhibited tumor cell derived angiogenesis. SAW may aid in treating prostate cancer and molecules important for SAW’s apoptotic and anti-angiogenic effects need to be determined.


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