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Inorganic selenium for treatment of cancer

A cancer, selenate technology, applied in drug combinations, organic active ingredients, sulfur/selenium/tellurium active ingredients, etc., can solve problems such as differences in tumor progression of human prostate tumor cells

Inactive Publication Date: 2007-12-12
VELACOR THERAPEUTICS PTY LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] However, significant differences in in vivo tumor progression of human prostate tumor cells have been noted depending on the selenium compound administered

Method used

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  • Inorganic selenium for treatment of cancer
  • Inorganic selenium for treatment of cancer
  • Inorganic selenium for treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] Inhibition of prostate tumor progression with sodium selenate through inhibition of protein kinase B / AKT activation

[0106] Materials and methods

[0107] cell culture

[0108] Cell culture experiments included the PC-3 cell line obtained from the American Type Culture Collection (Manassas, Virginia, USA). Cells are typically cultured with RPMI 1641 (Invitrogen) supplemented with 10% fetal bovine serum and 1% antibiotic / antimycotic cocktail (Invitrogen). At 37°C, 5% CO 2 maintain cells. Sodium selenate and selenomethionine (Sigma) were prepared into a 10 mM stock solution with distilled water, sterilized by filtration, and then diluted with culture medium for in vitro experiments.

[0109] Animal experiment

[0110] Animal experiments included the use of BALB / c nude mice. On the first day of the experiment, 6-week-old BALB / c nude mice were anesthetized with an intraperitoneal injection of ketamine 100 mg / kg and xylazine 20 mg / kg. Under a magnifying glass, ...

Embodiment 2

[0154] Reduced prostate tumor growth due to synergistic effect of sodium selenate and paclitaxel

[0155] Materials and methods

[0156] Will 1×10 6 Prostate tumor PC-3 cells were injected into the prostate of nude mice. After 3 days, 5 ppm of selenium in the form of sodium selenate was given to mice receiving selenate in the drinking water. Paclitaxel at 10 mg / kg in 10% Cremophor EL / 25% ethanol / 65% PBS solution was administered intraperitoneally to animals receiving paclitaxel once a week. 10 animals were used in each group. Five weeks after the injection, the animals were sacrificed, the prostates were removed, the attachments were dissected, and the tumors were weighed. Lymph node lesions in the retroperitoneal cavity were explored, and lymph nodes with a diameter greater than 0.5 mm were removed. The tumor was then sectioned in multiple layers at 50 μm slices, using the standard volumetric formula (a+b 2 / 2) Calculation of tumor volume from digitized images.

[01...

Embodiment 3

[0164] Comparison Test Between Selenate and Selenite

[0165] Materials and methods

[0166] Cytotoxic

[0167] Cytotoxicity after treatment with 5 μM or 50 μM sodium selenate or sodium selenite involves determination of cytotoxicity by trypan blue exclusion. will be 5×10 3 Human prostate cancer PC-3 cells were seeded in 24-well plates and treated with 5 μM or 50 μM selenate or selenite 8 hours later. A dose range of 5 μM or 50 μM is equivalent to 0.1 mg / kg-1.25 mg / kg. Cells were harvested 24, 48, 72, and 96 hours after the addition of selenate or selenite, and the percent viable cells were assessed by staining with trypan blue. The results are shown in Figure 9, which depicts the mean and SD of three independent experiments. Figure 9 shows that selenate is a cytostatic substance, while similar concentrations of selenite are cytotoxic. Therefore, selenite is not suitable for combination therapy in animals.

[0168] To differentiate the relative cytotoxic effects of ...

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Abstract

The present invention discloses the use of selenate or its pharmaceutically acceptable salts, especially in supranutritional amounts, in methods and compositions for inhibiting the growth or proliferation of tumor cells. The present invention also discloses the use of selenate or its pharmaceutically acceptable salts in combination with one or both of a hormone ablation therapy and a cytostatic agent or cytotoxic agent, for inhibiting the growth or proliferation of tumor cells. In certain embodiments, the methods of the invention are useful for treating or preventing cancers, especially cancers in which the Akt signaling pathway is activated, such as prostate cancer. Additionally, the present invention discloses the use of selenate or its pharmaceutically acceptable salts in combination with a hormone-ablation therapy and optionally a cytostatic agent or cytotoxic agent in methods and compositions for treating hormone-dependent cancers.

Description

field of invention [0001] The present invention generally relates to methods and compositions for the use of selenate or a pharmaceutically acceptable salt thereof, especially in supranutritive amounts, for inhibiting the growth or proliferation of tumor cells. The present invention also relates to the combination of selenate or a pharmaceutically acceptable salt thereof with at least one of hormone ablation therapy, cytostatic agent or cytotoxic agent to inhibit the growth or proliferation of tumor cells. In certain embodiments, the methods of the invention are useful in the treatment or prevention of cancer, particularly cancers in which the Akt signaling pathway is activated, such as prostate cancer. Furthermore, the present invention relates to methods and compositions of selenate or a pharmaceutically acceptable salt thereof for use in the treatment of hormone-dependent cancers in combination with hormone ablation therapy and optionally a cytostatic or cytotoxic agent. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K33/04A61P35/00
CPCA61K33/04A61K31/337A61K45/06A61P35/00A61K2300/00
Inventor N·科尔科兰C·霍文斯A·柯斯特洛
Owner VELACOR THERAPEUTICS PTY LTD
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