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Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1.

Lin HP, Lin CY, Huo C, Hsiao PH, Su LC, Jiang SS, Chan TM, Chang CH, Chen LT, Kung HJ, Wang HD, Chuu CP - Oncotarget (2015)

Bottom Line: CAPE treatment decreased Skp2 and Akt1 protein expression in LNCaP 104-R1 tumors as compared to control group.Overexpression of Skp2, or siRNA knockdown of p21Cip1, p27Kip1, or p53 blocked suppressive effect of CAPE treatment.Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT737 showed synergistic suppressive effects.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan, ROC.

ABSTRACT
Prostate cancer (PCa) patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant prostate cancer (CRPC) within 1-3 years. Treatment with caffeic acid phenethyl ester (CAPE) suppressed cell survival and proliferation via induction of G1 or G2/M cell cycle arrest in LNCaP 104-R1, DU-145, 22Rv1, and C4-2 CRPC cells. CAPE treatment also inhibited soft agar colony formation and retarded nude mice xenograft growth of LNCaP 104-R1 cells. We identified that CAPE treatment significantly reduced protein abundance of Skp2, Cdk2, Cdk4, Cdk7, Rb, phospho-Rb S807/811, cyclin A, cyclin D1, cyclin H, E2F1, c-Myc, SGK, phospho-p70S6kinase T421/S424, phospho-mTOR Ser2481, phospho-GSK3α Ser21, but induced p21Cip1, p27Kip1, ATF4, cyclin E, p53, TRIB3, phospho-p53 (Ser6, Ser33, Ser46, Ser392), phospho-p38 MAPK Thr180/Tyr182, Chk1, Chk2, phospho-ATM S1981, phospho-ATR S428, and phospho-p90RSK Ser380. CAPE treatment decreased Skp2 and Akt1 protein expression in LNCaP 104-R1 tumors as compared to control group. Overexpression of Skp2, or siRNA knockdown of p21Cip1, p27Kip1, or p53 blocked suppressive effect of CAPE treatment. Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT737 showed synergistic suppressive effects. Our finding suggested that CAPE treatment induced cell cycle arrest and growth inhibition in CRPC cells via regulation of Skp2, p53, p21Cip1, and p27Kip1.

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Related in: MedlinePlus

Gene expression of Tp53 in PCa patient oncomine database(A) Expression of Tp53 gene was detected by reporter probe 1974_s_at in 50 normal prostate gland samples and 52 prostate carcinoma samples from Singh prostate datasets using gene microarray [108]. (B) Expression of Tp53 gene was detected by reporter probe IMAGE:24415 in 21 normal prostate gland epithelial samples, 4 BPH (benign prostatic hyperplasia), 12 PIN (prostatic intraepithelial neoplasia), and 30 prostate carcinoma samples from Tomlins prostate datasets using gene microarray [109]. Data were downloaded from Oncomine (http://www.oncomine.com) without further processing.
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Figure 13: Gene expression of Tp53 in PCa patient oncomine database(A) Expression of Tp53 gene was detected by reporter probe 1974_s_at in 50 normal prostate gland samples and 52 prostate carcinoma samples from Singh prostate datasets using gene microarray [108]. (B) Expression of Tp53 gene was detected by reporter probe IMAGE:24415 in 21 normal prostate gland epithelial samples, 4 BPH (benign prostatic hyperplasia), 12 PIN (prostatic intraepithelial neoplasia), and 30 prostate carcinoma samples from Tomlins prostate datasets using gene microarray [109]. Data were downloaded from Oncomine (http://www.oncomine.com) without further processing.

Mentions: Analysis of Oncomine database suggested that PCa tumors expressed less Tp53 as compared to normal prostate epithelial tissues (Figure 13A, 13B). Since CAPE treatment significantly increased abundance of p53 protein, CAPE treatment is thus a potential effective therapy for PCa.


Caffeic acid phenethyl ester induced cell cycle arrest and growth inhibition in androgen-independent prostate cancer cells via regulation of Skp2, p53, p21Cip1 and p27Kip1.

Lin HP, Lin CY, Huo C, Hsiao PH, Su LC, Jiang SS, Chan TM, Chang CH, Chen LT, Kung HJ, Wang HD, Chuu CP - Oncotarget (2015)

Gene expression of Tp53 in PCa patient oncomine database(A) Expression of Tp53 gene was detected by reporter probe 1974_s_at in 50 normal prostate gland samples and 52 prostate carcinoma samples from Singh prostate datasets using gene microarray [108]. (B) Expression of Tp53 gene was detected by reporter probe IMAGE:24415 in 21 normal prostate gland epithelial samples, 4 BPH (benign prostatic hyperplasia), 12 PIN (prostatic intraepithelial neoplasia), and 30 prostate carcinoma samples from Tomlins prostate datasets using gene microarray [109]. Data were downloaded from Oncomine (http://www.oncomine.com) without further processing.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466643&req=5

Figure 13: Gene expression of Tp53 in PCa patient oncomine database(A) Expression of Tp53 gene was detected by reporter probe 1974_s_at in 50 normal prostate gland samples and 52 prostate carcinoma samples from Singh prostate datasets using gene microarray [108]. (B) Expression of Tp53 gene was detected by reporter probe IMAGE:24415 in 21 normal prostate gland epithelial samples, 4 BPH (benign prostatic hyperplasia), 12 PIN (prostatic intraepithelial neoplasia), and 30 prostate carcinoma samples from Tomlins prostate datasets using gene microarray [109]. Data were downloaded from Oncomine (http://www.oncomine.com) without further processing.
Mentions: Analysis of Oncomine database suggested that PCa tumors expressed less Tp53 as compared to normal prostate epithelial tissues (Figure 13A, 13B). Since CAPE treatment significantly increased abundance of p53 protein, CAPE treatment is thus a potential effective therapy for PCa.

Bottom Line: CAPE treatment decreased Skp2 and Akt1 protein expression in LNCaP 104-R1 tumors as compared to control group.Overexpression of Skp2, or siRNA knockdown of p21Cip1, p27Kip1, or p53 blocked suppressive effect of CAPE treatment.Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT737 showed synergistic suppressive effects.

View Article: PubMed Central - PubMed

Affiliation: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan, ROC.

ABSTRACT
Prostate cancer (PCa) patients receiving the androgen ablation therapy ultimately develop recurrent castration-resistant prostate cancer (CRPC) within 1-3 years. Treatment with caffeic acid phenethyl ester (CAPE) suppressed cell survival and proliferation via induction of G1 or G2/M cell cycle arrest in LNCaP 104-R1, DU-145, 22Rv1, and C4-2 CRPC cells. CAPE treatment also inhibited soft agar colony formation and retarded nude mice xenograft growth of LNCaP 104-R1 cells. We identified that CAPE treatment significantly reduced protein abundance of Skp2, Cdk2, Cdk4, Cdk7, Rb, phospho-Rb S807/811, cyclin A, cyclin D1, cyclin H, E2F1, c-Myc, SGK, phospho-p70S6kinase T421/S424, phospho-mTOR Ser2481, phospho-GSK3α Ser21, but induced p21Cip1, p27Kip1, ATF4, cyclin E, p53, TRIB3, phospho-p53 (Ser6, Ser33, Ser46, Ser392), phospho-p38 MAPK Thr180/Tyr182, Chk1, Chk2, phospho-ATM S1981, phospho-ATR S428, and phospho-p90RSK Ser380. CAPE treatment decreased Skp2 and Akt1 protein expression in LNCaP 104-R1 tumors as compared to control group. Overexpression of Skp2, or siRNA knockdown of p21Cip1, p27Kip1, or p53 blocked suppressive effect of CAPE treatment. Co-treatment of CAPE with PI3K inhibitor LY294002 or Bcl-2 inhibitor ABT737 showed synergistic suppressive effects. Our finding suggested that CAPE treatment induced cell cycle arrest and growth inhibition in CRPC cells via regulation of Skp2, p53, p21Cip1, and p27Kip1.

Show MeSH
Related in: MedlinePlus