Chemoprevention of Prostate Cancer

Klein, Eric A.

doi:10.1146/annurev.med.57.121304.131435

Cited by 42 publications

(21 citation statements)

References 42 publications

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“…However, many patients eventually develop castration resistant PCa, for which current treatment options are only palliative. The prevalence, long latency, morbidity and mortality associated with PCa have generated significant interest in developing agents for chemoprevention of the disease [3].…”

Section: Introductionmentioning

confidence: 99%

Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

et al. 2014

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The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (calcitriol) has antiproliferative effects in non-aggressive prostate cancer, however, its effects in more aggressive model systems are still unclear. In these studies, effects of calcitriol and a less-calcemic vitamin D analog, QW-1624F2-2 (QW), were tested in vivo, using the aggressive autochthonous transgenic adenocarcinoma of mouse prostate (TRAMP) model. To study prevention of androgen-stimulated prostate cancer, vehicle, calcitriol (20 µg/kg), or QW (50 µg/kg) were administered to 4 week-old TRAMP mice intraperitoneal (i.p.) 3×/week on a MWF schedule for 14 weeks. Calcitriol and QW slowed progression of prostate cancer as indicated by reduced urogenital tract (p = 0.0022, calcitriol; p = 0.0009, QW) and prostate weights (p = 0.0178, calcitriol; p = 0.0086, QW). However, only calcitriol increased expression of the pro-differentiation marker, cadherin 1 (p = 0.0086), and reduced tumor proliferation (p = 0.0467). By contrast, neither vitamin D analog had any effect on castration resistant prostate cancer in mice treated pre- or post-castration. Interestingly, although vitamin D showed inhibitory activity against primary tumors in hormone-intact mice, distant organ metastases seemed to be enhanced following treatment (p = 0.0823). Therefore, TRAMP mice were treated long-term with calcitriol to further examine effects on metastasis. Calcitriol significantly increased the number of distant organ metastases when mice were treated from 4 weeks-of-age until development of palpable tumors (20–25 weeks-of-age)(p = 0.0003). Overall, data suggest that early intervention with vitamin D in TRAMP slowed androgen-stimulated tumor progression, but prolonged treatment resulted in development of a resistant and more aggressive disease associated with increased distant organ metastasis.

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Section: Introductionmentioning

confidence: 99%

Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

et al. 2014

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“…This geographical distribution has been attributed to the difference in dietary pattern, which is recognized as one of the major etiologic factors responsible for a variation in PCa incidence and mortality between Asian and Western male populations [2][3][4][5]. The major percentage of the dietary composition in the industrialized Western countries includes highly processed foods rich in meat, dairy products, and worldwide have directed considerable efforts toward the identification of dietary and/or nondietary naturally occurring chemical agents which would be beneficial for both prevention and intervention of PCa [7][8][9]. One such dietary agent is inositol hexaphosphate (IP6) or phytic acid, which is abundantly present in high fiber content diets, most cereals, legumes, nuts, and soybean [10,11].…”

Section: Introductionmentioning

confidence: 99%

Inositol hexaphosphate downregulates both constitutive and ligand-induced mitogenic and cell survival signaling, and causes caspase-mediated apoptotic death of human prostate carcinoma PC-3 cells

Raina

Agarwal

et al. 2009

Mol. Carcinog.

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Constitutively active mitogenic and pro-survival signaling cascades due to aberrant expression and interaction of growth factors and their receptors are well documented in human prostate cancer (PCa). EGF and IGF-1 are potent mitogens that regulate proliferation and survival of PCa cells via autocrine and paracrine loops involving both MAPK- and Akt-mediated signaling. Accordingly, here we assessed the effect of inositol hexaphosphate (IP6) on constitutive and ligand (EGF and IGF-1)-induced biological responses and associated signaling cascades in advanced and androgen-independent human PCa PC-3 cells. Treatment of PC-3 cells with 2 mM IP6 strongly inhibited both growth and proliferation and decreased cell viability; similar effects were also observed in other human PCa DU145 and LNCaP cells. IP6 also caused a strong apoptotic death of PC-3 cells together with caspase 3 and PARP cleavage. Mechanistic studies showed that biological effects of IP6 were associated with inhibition of both constitutive and ligand-induced Akt phosphorylation together with a decrease in total Akt levels, but a differential inhibitory effect on MAPKs ERK1/2, JNK1/2 and p38 under constitutive and ligand-activated conditions. Under similar condition, IP6 also inhibited AP-1 DNA binding activity and decreased nuclear levels of both phospho and total c-Fos and c-Jun. Together, these findings for the first time establish IP6 efficacy in inhibiting aberrant EGFR or IGF-1R pathway-mediated sustained growth promoting and survival signaling cascades in advanced and androgen-independent human PCa PC-3 cells, which might have translational implications in advanced human PCa control and management.

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“…Growing evidence from epidemiologic surveys and case-control studies show that diet and lifestyle play an essential role in PCa development and progression [44,45]. It is also recognized in recent years that many nutrients and herbs have significant promise in controlling and managing PCa by slowing the progression and reducing recurrence via targeting survival and apoptotic machinery [4,44–46].…”

Section: Discussionmentioning

confidence: 99%

Procyanidin B2 3,3^″-di-O-gallate, a Biologically Active Constituent of Grape Seed Extract, Induces Apoptosis in Human Prostate Cancer Cells Via Targeting NF-κB, Stat3, and AP1 Transcription Factors

Tyagi¹,

Raina²,

Shrestha³

et al. 2013

Nutrition and Cancer

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Recently, we identified procyanidin B2 3,3″-di-O-gallate (B2G2) as most active constituent of grape seed extract (GSE) for efficacy against prostate cancer (PCa). Isolating large quantities of B2G2 from total GSE is labor intensive and expensive, thereby limiting both efficacy and mechanistic studies with this novel anti-cancer agent. Accordingly, here we synthesized gram-scale quantities of B2G2, compared it with B2G2 isolated from GSE for possible equivalent biological activity, and conducted mechanistic studies. Both B2G2 preparations inhibited cell growth, decreased clonogenicity, and induced cell cycle arrest and apoptotic death, comparable to each other, in various human PCa cell lines. Mechanistic studies focusing on transcription factors involved in apoptotic and survival pathways revealed that B2G2 significantly inhibits NF-κB and AP1 transcriptional activity and nuclear translocation of Stat3 in PCa cell lines, irrespective of their functional androgen receptor status. B2G2 also decreased survivin expression which is regulated by NF-κB, AP1 and Stat3, and increased cleaved PARP level. In summary, we report B2G2 chemical synthesis at gram-quantity with equivalent biological efficacy against human PCa cell lines and same molecular targeting profiles at key transcription factors level. The synthetic B2G2 will stimulate more research on prostate and possibly other malignancies in preclinical models and clinical translation.

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Chemoprevention of Prostate Cancer

Cited by 42 publications

References 42 publications

Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

Inositol hexaphosphate downregulates both constitutive and ligand-induced mitogenic and cell survival signaling, and causes caspase-mediated apoptotic death of human prostate carcinoma PC-3 cells

Procyanidin B2 3,3^″-di-O-gallate, a Biologically Active Constituent of Grape Seed Extract, Induces Apoptosis in Human Prostate Cancer Cells Via Targeting NF-κB, Stat3, and AP1 Transcription Factors

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Chemoprevention of Prostate Cancer

Cited by 42 publications

References 42 publications

Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

Inositol hexaphosphate downregulates both constitutive and ligand-induced mitogenic and cell survival signaling, and causes caspase-mediated apoptotic death of human prostate carcinoma PC-3 cells

Procyanidin B2 3,3″-di-O-gallate, a Biologically Active Constituent of Grape Seed Extract, Induces Apoptosis in Human Prostate Cancer Cells Via Targeting NF-κB, Stat3, and AP1 Transcription Factors

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Procyanidin B2 3,3^″-di-O-gallate, a Biologically Active Constituent of Grape Seed Extract, Induces Apoptosis in Human Prostate Cancer Cells Via Targeting NF-κB, Stat3, and AP1 Transcription Factors