Application of cepharanthine and salts thereof as ferroptosis inducer in preparation of anti-tumor drug

An anti-tumor drug, the technology of fenugreek, applied in the field of medicine, can solve problems such as unreported, and achieve the effects of good safety, significant anti-cancer and anti-resistance effects, and good application prospects

Pending Publication Date: 2020-06-05
GUANGZHOU JINAN BIOMEDICINE RES & DEV CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Cepharanthine hydrochloride (CH) is a semi-synthetic compound obtained by salinizing cepharanthine hydrochloride extracted from Stephania plant Stephania chinensis. Its structural formula is: At present, there is no report on the effect of stephenine as a ferroptosis inducer on tumor-related aspects at home and abroad.

Method used

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  • Application of cepharanthine and salts thereof as ferroptosis inducer in preparation of anti-tumor drug
  • Application of cepharanthine and salts thereof as ferroptosis inducer in preparation of anti-tumor drug
  • Application of cepharanthine and salts thereof as ferroptosis inducer in preparation of anti-tumor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Embodiment 1, the influence of different concentrations of stephine hydrochloride on the survival of prostate cancer cells

[0022] S1. Use an electronic balance to weigh stephine hydrochloride powder and place it in a centrifuge tube, then add dimethyl sulfoxide (DMSO) to dissolve it, prepare a mother solution with a concentration of 100mM, and then dilute it into different concentrations with DMSO, hydrochloric acid The concentrations of Stephanine were 1 μM, 20 μM, 40 μM, 80 μM and 100 μM, which were respectively added to DMEM / F12 medium containing 10% fetal bovine serum, and the experiment was ready for use;

[0023] S2. Select four prostate cancer cells DU145 (purchased from the ATCC cell bank), LNcap (purchased from the ATCC cell bank), PC-3 (purchased from the ATCC cell bank), and PC-3M (purchased from the National Experimental Cell Resource Sharing Platform) Cells, prostate cancer cells were digested with a digestion solution containing 0.075wt.% type I collagen...

Embodiment 2

[0027] Example 2. Detection of the effect of stephanine hydrochloride on the death pathway of prostate cancer cells

[0028] S1. Using the mother solution prepared in Example 1 with a concentration of 100 mM, and then diluting it into different concentrations with the medium, the final concentrations of stephine hydrochloride are 10 μM and 20 μM respectively, and the cells are respectively cultured, divided into two groups, and then set One group of DMSO is used as a blank control group (expressed as control), and the dose of DMSO added is the same as that of stephine hydrochloride, and the experiment is for use;

[0029] S2. Inoculate the prostate cancer cell LNcap suspension prepared in step S2 of Example 1 in a 6-well plate, and inoculate 30×10 cells in each well. 4 cells / ml, the prostate cancer cells were cultured with the 3 groups of culture media prepared in Step S1 of Example 2, and when they were cultured for 24h and 48h, the prostate cancer cells were collected into c...

Embodiment 3

[0031] Example 3, Determination of the Effect of Stephanine Hydrochloride on Active Oxygen in Prostate Cancer Cell LNcap

[0032] S1. Diluted according to Example 2 to obtain stephine hydrochloride with a concentration of 10 μM and 20 μM respectively, respectively added to DMEM / F12 medium containing 10% fetal bovine serum, divided into two groups, and then set a group of DMSO as a blank control group (expressed as control), the dose of DMSO added was the same as the dose of stephine hydrochloride, the prostate cancer cell LNcap suspension prepared in Example 2 was inoculated in a 6-well plate, and each well was inoculated with 30 × 10 cells. 4 Individual / ml, carry out prostate cancer cell culture with 3 groups of mediums that the present embodiment makes, experiment stand-by;

[0033] S2. Dilute the reactive oxygen species detection probe DCFH-DA with serum-free medium at a ratio of 1:1000, so that the final concentration is 10 μM. Prostate cancer cells LNcap cultured in 6-we...

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Abstract

The invention relates to the technical field of medicines and provides application of cepharanthine and salts thereof as a ferroptosis inducer in preparation of an anti-tumor drug. As found, natural products, namely cepharanthine and salts thereof, which are already applied clinically for many years can induce ferroptosis of prostate cancer cells in expressive ways of active oxygen increase, accumulation of lipid peroxides, decrease in the expression level of GPX4, structural changes in mitochondria, etc. Therefore, cepharanthine and salts thereof have good anti-cancer effects and provide a new effective therapeutic drug for tumor disease patients.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to the application of stephine and its salt as a ferroptosis inducer in the preparation of antitumor drugs. Background technique [0002] Apoptosis is the most well-studied type of cell death, however, in recent years, in addition to apoptosis, many other forms of cell death have been discovered, including autophagic cell death, ferroptosis, pyroptosis, glutamate apoptosis and Exosome-associated cell death. Traditional cancer therapy mainly targets apoptosis, however, many cancer cells are chemoresistant and defective in apoptosis induction, most mechanisms controlling apoptotic and non-apoptotic cell death are also regulated independently, and cells may also Various stresses are experienced, leading to apoptotic and non-apoptotic cell death. Most of the tumors were treated with surgical resection and radiotherapy in the early stages, and multimodal treatment combined with surger...

Claims

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Application Information

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IPC IPC(8): A61K31/4741A61P35/00
CPCA61K31/4741A61K9/0019A61P35/00
Inventor 王一飞王瑶黄泽秀
Owner GUANGZHOU JINAN BIOMEDICINE RES & DEV CENT
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