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Treatment of benign prostatic hyperplasia using energolytic agents

A technology of benign prostatic hyperplasia and dispersant, applied in the field of biology, can solve the problems of not reducing the size of the prostate and unsatisfied drugs

Inactive Publication Date: 2006-02-22
THRESHOLD PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this class of drug reduces symptoms more quickly than the first drug, it does not reduce the size of the prostate, or prevent the prostate from becoming larger, which can lead to eventual surgical intervention
[0005] Therefore, there is a clear, unmet need for drugs that can treat the underlying disease state of BPH without serious side effects

Method used

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  • Treatment of benign prostatic hyperplasia using energolytic agents
  • Treatment of benign prostatic hyperplasia using energolytic agents
  • Treatment of benign prostatic hyperplasia using energolytic agents

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

Lonidamine reduces HIF-1α expression in prostate cells

[0109] This example shows the effect of lonidamine treatment on the expression of HIF-la in two cell lines derived from human prostate cancer metastases. LNCaP is a citrate producing cell (ATTC No. CRL-1740), and PC3 is a citrate oxidizing cell (ATTC No. CRL-1435). See Franklin et al; 1995, Endocrine 3:603-607. Cells can be obtained from the American Type Culture Collection (ATCC) P.O. Box 1549, Manassas, VA 20108 USA.

[0110] As shown in Figures 3 and 4, lonidamine treatment reduced HIF-1α protein levels, as detected in nuclear (NE) and whole cell extract (WCE) preparations. Inhibition was dose-dependent and observed under normoxia (PC3 cells only) and hypoxia (LNCaP cells and PC3 cells). The effect of lonidamine was specific to the HIF-1α subunit and, except at the 800 μM concentration, had no detectable effect on protein levels of actin, caspase3, NF-κB, or IκBα under the conditions tested to the inhibitory...

Embodiment 2

Lonidamine induces apoptosis in citrate producing cells

[0113] To determine whether apoptosis occurs in lonidamine-treated cells, the effect of lonidamine on citrate-producing cells (LNCaP) and citrate-oxidizing cells (PC3) was evaluated. As shown in Figure 4, lonidamine induced the activation of caspase 3 in citrate producing cells (LNCaP) to a much greater extent than in citrate oxidizing cells (PC3). Activation of caspase3 is a time-dependent process (Fig. 5).

[0114] The effect of lonidamine was also examined in primary cultures of prostate epithelial cells, which accumulate citrate, or in primary cultures of prostate stromal cells, which do not accumulate citrate. As shown in Figure 5, lonidamine induced apoptosis in a dose-dependent manner only in prostate epithelial cells. In contrast, no induction of apoptosis was observed in prostate stromal cells after lonidamine treatment.

method

[0115] Immunoblot: Immunoblot was performed as described in Example ...

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Abstract

The invention provides a method for treatment or prophylaxis of benign prostatic hyperplasia by administration of an agent that interferes with energy metabolism, particularly the production of ATP and NADH / NADPH, in prostate epithelial cells.

Description

[0001] Cross References to Related Applications [0001] This application claims the benefit of the following U.S. Provisional Applications: U.S. Provisional Application Nos. 60 / 496,163 (filed August 18, 2003), 60 / 488,265 (filed July 18, 2003), 60 / 472,907 (filed May 2003) 22), 60 / 460,012 (filed 2 April 2003), 60 / 458,846 (filed 28 March 2003), 60 / 458,665 (filed 28 March 2003), 60 / 458,663 60 / 442,344 (filed January 23, 2003), and 60 / 441,110 (filed January 17, 2003), each of which is hereby incorporated in its entirety , used as a reference for all topics. technical field [0002] The present invention relates to the treatment and prevention of benign prostatic hyperplasia, and has applications in the fields of medicine and related fields, including but not limited to the fields of chemistry, medical chemistry, and biology. Background technique [0003] Benign Prostatic Hyperplasia (BPH), a disease in which abnormal growths of epithelial cells in the prostate gla...

Claims

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Application Information

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IPC IPC(8): A61K31/70G01N33/567C12Q1/06
Inventor G・提马思H・E・塞利科F・孟
Owner THRESHOLD PHARM INC
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