scholarly journals Supercritical Fluid Extraction of Citrus iyo Hort. ex Tanaka Pericarp Inhibits Growth and Induces Apoptosis Through Abrogation of STAT3 Regulated Gene Products in Human Prostate Cancer Xenograft Mouse Model

2016 ◽  
Vol 16 (2) ◽  
pp. 227-243 ◽  
Author(s):  
Chulwon Kim ◽  
Il Ho Lee ◽  
Ho Bong Hyun ◽  
Jong-Chan Kim ◽  
Rajendra Gyawali ◽  
...  

Activation of signal transducer and activator of transcription 3 (STAT3) is well known to play a major role in the cell growth, survival, proliferation, metastasis, and angiogenesis of various cancer cells. Most of the citrus species offer large quantities of phytochemicals that have beneficial effects attributed to their chemical components. Our study was carried out to evaluate the anticancer effects of the pericarp of Iyokan ( Citrus iyo Hort. ex Tanaka), locally known as yeagam in Korea, through modulation of the STAT3 signaling pathway in both tumor cells and a nude mice model. The effect of supercritical extracts of yeagam peel (SEYG) on STAT3 activation, associated protein kinases, STAT3-regulated gene products, cellular proliferation, and apoptosis was examined. The in vivo effect of SEYG on the growth of DU145 human prostate xenograft tumors in athymic nu/nu male mice was also investigated. We found SEYG exerted substantial inhibitory effect on STAT3 activation in human prostate cancer DU145 cells as compared to other tumor cells analyzed. SEYG inhibited proliferation and downregulated the expression of various STAT3-regulated gene products such as bcl-2, bcl-xL, survivin, IAP-1/2, cyclin D1, cyclin E, COX-2, VEGF, and MMP-9. This correlated with an increase in apoptosis as indicated by an increase in the expression of p53 and p21 proteins, the sub-G1 arrest, and caspase-3-induced PARP cleavage. When administered intraperitoneally, SEYG reduced the growth of DU145 human prostate xenograft tumors through downmodulation of STAT3 activation in athymic nu/nu male mice. Overall, these results suggest that SEYG extract has the potential source of STAT3 inhibitors that may have a potential in chemoprevention of human prostate cancer cells.

2005 ◽  
Vol 230 (3) ◽  
pp. 171-179 ◽  
Author(s):  
Holly L. Hantz ◽  
Leeanne F. Young ◽  
Keith R. Martin

Prostate cancer is the second leading cause of cancer deaths among men in the United States. Studies show that people with diets rich in tomato-based foods have reduced risks of cancer, viz., prostate cancer. This is attributed, in part, to lycopene, the most abundant carotenoid in tomatoes. Thus, we studied the effect of lycopene at physiologically attainable concentrations on apoptosis, cellular proliferation, and necrosis in LNCaP human prostate cancer cells. Cells at 37°C and >80% confluency were treated with media alone (0.32% tetrahydrofuran vehicle) or with increasing concentrations (0.3–3.0 μM) of lycopene overnight. After washing monolayers, analyses by high-performance liquid chromatography (HPLC) showed that cellular accumulation of lycopene was 5.5 ± 0.8, 14.0 ± 3.2, and 36.7 ± 12.3 pmole/106 cells for 0.3, 1.0, and 3.0 μM, respectively, and not detected in control cells. Lycopene did not alter cellular proliferation because bromodeoxyuridine (BrdU) incorporation and cell numbers were identical among groups. However, results of a 3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay showed that mitochondrial function decreased 61%–83% with increasing concentrations of lycopene (P < 0.001). Cytotoxicity and necrosis did not contribute to this effect because lactate dehydrogenase (LDH) release (1.5%–1.8%) and trypan blue exclusion (89%–93%) were similar. Subsequently, we demonstrated that increasing concentrations of lycopene significantly (P < 0.05) reduced mitochondrial transmembrane potential, induced the release of mitochondrial cytochrome c, and increased annexin V binding, confirming induction of apoptosis. Thus, lycopene at physiologically relevant concentrations did not affect cellular proliferation or promote necrosis but clearly altered mitochondrial function and induced apoptosis in LNCaP human prostate cancer cells.


BMC Urology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Martha E. Cancino-Marentes ◽  
Georgina Hernández-Flores ◽  
Pablo Cesar Ortiz-Lazareno ◽  
María Martha Villaseñor-García ◽  
Eduardo Orozco-Alonso ◽  
...  

Abstract Background Prostate cancer is one of the most frequently diagnosed types of cancers worldwide. In its initial period, the tumor is hormone-sensitive, but in advanced states, it evolves into a metastatic castration-resistant tumor. In this state, chemotherapy with taxanes such as Docetaxel (DTX) comprises the first line of treatment. However, the response is poor due to chemoresistance and toxicity. On the other hand, Pentoxifylline (PTX) is an unspecific inhibitor of phosphodiesterases; experimental, and clinically it has been described as sensitizing tumor cells to chemotherapy, increasing apoptosis and decreasing senescence. We study whether the PTX sensitizes prostate cancer cells to DTX for greater effectiveness. Methods PC3 human prostate cancer cells were treated in vitro at different doses and times with PTX, DTX, or their combination. Viability was determined by the WST-1 assay by spectrophotometry, cell cycle progression, apoptosis, generic caspase activation and senescence by flow cytometry, DNA fragmentation and caspases-3, -8, and -9 activity by ELISA. Results We found that PTX in PC3 human prostate cancer cells induces significant apoptosis per se and increases that generated by DTX, while at the same time it reduces the senescence caused by the chemotherapy and increases caspases-3,-8, and -9 activity in PTX + DTX-treated cells. Both treatments blocked the PC3 cell in the G1 phase. Conclusions Our results show that PTX sensitizes prostate tumor cells to apoptosis induced by DTX. Taken together, the results support the concept of chemotherapy with rational molecular bases.


Oncogene ◽  
2000 ◽  
Vol 19 (5) ◽  
pp. 670-679 ◽  
Author(s):  
J Tsihlias ◽  
W Zhang ◽  
N Bhattacharya ◽  
M Flanagan ◽  
L Klotz ◽  
...  

2015 ◽  
Vol 5 (1) ◽  
pp. 17 ◽  
Author(s):  
Brendan T. McKeown ◽  
Robert A. R. Hurta

Background: Prostate cancer is the most commonly diagnosed form of cancer in men in Canada and the United States. Both genetic and environmental factors contribute to the development and progression of many cancers, including prostate cancer.Context and purpose of this study: This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on cellular proliferation and proliferation-linked activities of PC3 human prostate cancer cells in vitro.Results: PC3 cells exposed to magnolol at a concentration of 80 μM for 6 hours exhibited decreased protein expression of ornithine decarboxylase, a key regulator in polyamine biosynthesis, as well as affecting the expression of other proteins involved in polyamine biosynthesis and catabolism. Furthermore, protein expression of the R2 subunit of ribonucleotide reductase, a key regulatory protein associated with DNA synthesis, was significantly decreased. Finally, the MAPK (mitogen-activated protein kinase), PI3K (phosphatidylinositol 3-kinase), NFκB (nuclear factor of kappa-light-chain-enhancer of activated B cells) and AP-1 (activator protein 1) cellular signaling pathways were assayed to determine which, if any, of these pathways magnolol exposure would alter. Protein expressions of p-JNK-1 and c-jun were significantly increased while p-p38, JNK-1/2, PI3Kp85, p-PI3Kp85, p-Akt, NFκBp65, p-IκBα and IκBα protein expressions were significantly decreased.Conclusions: These alterations further support the anti-proliferative effects of magnolol on PC3 human prostate cancer cells in vitro and suggest that magnolol may have potential as a novel anti-prostate cancer agent.Key Words: prostate cancer cells, magnolol, polyamines, MAPK, PI3K, NFκB


2010 ◽  
Vol 5 (2) ◽  
pp. 178-189
Author(s):  
Hiroki Shima ◽  
Shingo Yamamoto ◽  
Jun Qiu ◽  
Mayumi Shincho ◽  
Seiichi Hirota ◽  
...  

AbstractWe introduce a new effective method to control hormone-refractory prostate cancer cells using an activated rubber/resin form (RB), far-infrared ray (FIR) emitter, with or without sodium butyrate treatment (NaB). The growth of three human prostate cancer cell lines (Du145, PC-3 and LNCaP) was suppressed in vitro and vivo by FIR, and the cells were eradicated with FIR + 3 mM NaB. G1 arrest and apoptotic pathway proteins were induced by FIR with elevated expressions of apoptosis-related transcripts in cDNA microarray. RB reflects and radiates in the wavelengths of about 4 to 25 µm in the FIR that work to suppress the growth of human prostate cancer cells. Accordingly, this technique may be used as a new therapeutic treatment in hormone-refractory prostate cancer.


Sign in / Sign up

Export Citation Format

Share Document