Effect of prostatic inhibin peptide (PIP) on prostate cancer cell growth in vitro and in vivo

Garde, Seema V.; Sheth, A. R.; Porter, Arthur T.; Pienta, Kenneth J.

doi:10.1002/pros.2990220305

Cited by 38 publications

(23 citation statements)

References 19 publications

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“…Although these studies clearly show apoptosis to be one of the mechanisms responsible for the effects of PCK3145, results from this study provide evidence for additional mechanisms that could also play an important role. Previous studies have shown that PSP-94 can down-regulate the levels of folliclestimulating hormone, which is known to decrease intracellular calcium (41)(42)(43). This pathway therefore represents one potential mechanism responsible for the ability of PCK3145 to decrease plasma PTHrP as reported in this study.…”

Section: Discussionsupporting

confidence: 69%

A Synthetic 15-mer Peptide (PCK3145) Derived from Prostate Secretory Protein Can Reduce Tumor Growth, Experimental Skeletal Metastases, and Malignancy-Associated Hypercalcemia

et al. 2004

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In previous studies, we have shown that prostate secretory protein (PSP-94) can reduce prostate cancer growth in vivo. In the current study, we identified the amino acid sequence of PSP-94 that is required for eliciting this response. For these studies, we used rat prostate cancer Mat Ly Lu cells overexpressing parathyroid hormone-related protein (PTHrP), which is the main pathogenetic factor responsible for hypercalcemia of malignancy. Synthetic peptides corresponding to amino acids 7-21 (PCK721), 31-45 (PCK3145), and 76 -94 (PCK7694) of PSP-94 were synthesized. Only PCK3145 showed a significant reduction in tumor cell proliferation. For in vivo studies, syngenic male Copenhagen rats were inoculated s.c. with Mat Ly Lu cells overexpressing PTHrP into the right flank or into the left ventricle via intracardiac injection, which results in experimental metastases to the lumbar vertebrae causing hind-limb paralysis. Animals were infused with different doses (1, 10, and 100 g/kg/ day) of peptides for 15 days, and the effect of these treatments on tumor volume, skeletal metastases, or development of hind-limb paralysis was determined. Treatment with PCK3145 resulted in a dose-dependent decrease in tumor volume and delay in the development of skeletal metastases. Bone histomorphometry showed that after intracardiac inoculation of tumor cells, the highest dose of PCK3145 (100 g/kg/day) resulted in reducing skeletal tumor burden, which delayed the development of hindlimb paralysis. Treatment with PCK3145 led to reduction of plasma calcium and PTHrP levels and a significant decrease in PTHrP levels in the primary tumors and in vertebrae of experimental animals. These effects of PCK3145 were due to its ability to promote tumor cell apoptosis. Collectively, the results of these studies have demonstrated the ability of a small peptide derived from PSP-94 to reduce tumor volume and experimental skeletal metastases-results that will be highly beneficial in the continued development of this peptide as a novel therapeutic agent for patients with hormone refractory, late-stage prostate cancer.

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Section: Discussionsupporting

confidence: 69%

A Synthetic 15-mer Peptide (PCK3145) Derived from Prostate Secretory Protein Can Reduce Tumor Growth, Experimental Skeletal Metastases, and Malignancy-Associated Hypercalcemia

et al. 2004

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“…Prostate cancer patients with positive PSP94 expression have a significantly better prognosis than those with negative expression [7]. This latter observation suggests that PSP94 may play an inhibitory role in prostate cancer cell growth, which is supported by our own [8] as well as the data of others [9] showing that exogenous PSP94 could inhibit the growth of rat Dunning prostate tumor cells. The results from the present study demonstrate that PSP94, in a time-and dosedependent manner, inhibited PC3 cell (an androgenindependent and metastatic prostate cancer cell line) growth in vitro, clonogenic survival in soft agar, and growth of PC3 xenografts in athymic mice.…”

Section: Introductionsupporting

confidence: 64%

“…In vivo xenograft experiments confirmed the efficacy of PSP94 in retarding tumor growth, which may have resulted from a combination of both reduced cell proliferation and survival. It should be pointed out that in one of our earlier studies [8], PSP94 did not inhibit the growth of PC3 cells, although the protein inhibited the proliferation of rat Dunning MAT LyLu cells. This discrepancy may have resulted from the use of relatively impure preparations of PSP94 in the earlier study.…”

Section: Discussionmentioning

confidence: 94%

Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis

Garde

Basrur

Li³

et al. 1999

Prostate

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“…Also, FSH levels are significantly higher in men with more advanced PCa [Heracek et al 2007]. Finally, endogenous compounds such as prostatic inhibin peptide (PIP) may inhibit PCa growth by inhibiting FSH [Garde et al 1993], and PIP expression is reduced in PCa [Zhang et al 1999]. Indeed, FSH-R may have a potential functional role in angiogenesis and the development of metastatic disease [Gartrell et al 2012].…”

Section: Effects On Follicle-stimulating Hormonementioning

confidence: 99%

Experience with degarelix in the treatment of prostate cancer

Shore

2012

Therapeutic Advances in Urology

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Degarelix is a gonadotrophin-releasing hormone (GnRH) antagonist for the firstline treatment of androgen-dependent advanced prostate cancer. It has a direct mechanism of action that blocks the action of GnRH on the pituitary with no initial surge in gonadotrophin or testosterone levels. Degarelix is the most extensively studied and widely available GnRH antagonist worldwide. Clinical studies have demonstrated similar efficacy to the GnRH agonist leuprolide in achieving testosterone suppression in patients with prostate cancer. However, degarelix produces a faster suppression of testosterone and prostate-specific antigen (PSA), with no testosterone surge or microsurges, thus preventing the risk of clinical flare in advanced disease. Clinical trials have demonstrated that degarelix can offer improved disease control when compared with a GnRH agonist in terms of superior PSA progression-free survival (suggesting that degarelix likely delays progression to castration-resistant disease), and a more significant impact on bone serum alkaline phosphatase and follicle-stimulating hormone. Degarelix is generally well tolerated, with no reports of systemic allergic reactions in any clinical studies. In conclusion, degarelix offers clinicians a rational first-line hormonal monotherapy option for the management of advanced prostate cancer.

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Effect of prostatic inhibin peptide (PIP) on prostate cancer cell growth in vitro and in vivo

Cited by 38 publications

References 19 publications

A Synthetic 15-mer Peptide (PCK3145) Derived from Prostate Secretory Protein Can Reduce Tumor Growth, Experimental Skeletal Metastases, and Malignancy-Associated Hypercalcemia

A Synthetic 15-mer Peptide (PCK3145) Derived from Prostate Secretory Protein Can Reduce Tumor Growth, Experimental Skeletal Metastases, and Malignancy-Associated Hypercalcemia

Prostate secretory protein (PSP94) suppresses the growth of androgen-independent prostate cancer cell line (PC3) and xenografts by inducing apoptosis

Experience with degarelix in the treatment of prostate cancer

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