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Pharmaceutical composition for preventing or treating cancer, comprising gossypol, phenformin, and anticancer agent

A technology of phenformin and its composition, which is applied in the field of anticancer agents, can solve problems such as unreported anticancer effects, and achieve the effect of significant inhibition of cancer cell proliferation and tumor growth

Pending Publication Date: 2021-03-26
国立がんセンター
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] As described above, the respective anticancer effects of gossypol and phenformin are known, but it has not been reported that they can exhibit higher active anticancer effects

Method used

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  • Pharmaceutical composition for preventing or treating cancer, comprising gossypol, phenformin, and anticancer agent
  • Pharmaceutical composition for preventing or treating cancer, comprising gossypol, phenformin, and anticancer agent
  • Pharmaceutical composition for preventing or treating cancer, comprising gossypol, phenformin, and anticancer agent

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Experimental program
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Embodiment approach

[0052] Hereinafter, the present invention will be provided in more detail.

[0053] The present invention provides a pharmaceutical composition for preventing or treating cancer, which comprises gossypol, phenformin and an anticancer agent as active ingredients, wherein the anticancer agent is sorafenib, vero Any of vemurafenib, irinotecan, cisplatin, paclitaxel, or doxorubicin.

[0054] The "gossypol" of the composition provided by the invention acts as an inhibitor of ALDH expression and cell activity. Specifically, gossypol acts as an inhibitor of ALDH expression and activity in the intracellular serine-folate mechanism in which ALDH produces NDAH and ATP from it, leading to ATP starvation in cells and killing cancer cells. Gossypol has the structure of the following formula 1:

[0055] [Formula 1]

[0056]

[0057] The "phenformin" of the composition provided by the present invention acts as an inhibitor of mitochondrial complex I in cells. Specifically, phenformin ...

Embodiment 1

[0087] Screening of anticancer agents showing synergistic effect by combination therapy with gossypol and phenformin in renal cell carcinoma

[0088] In the present invention, an attempt was made to screen a combination of anticancer agents capable of exhibiting a synergistic effect of anticancer effects when mixed and treated with conventional anticancer agents. Therefore, an anticancer agent was selected to enhance the anticancer effect by a triple combination obtained by mixing gossypol and phenformin and other anticancer agents. First, in order to select a combination that can exhibit a synergistic effect of anticancer effects on renal cancer, in addition to gossypol and phenformin, sorafenib, sunitinib, and pazopanib ) was also selected as a candidate anticancer agent for each test drug.

[0089] Specifically, when culturing the ACHN cell line or the CAKI-1 cell line of the kidney cancer cell line, each cell was seeded in a 96-well plate at a density of 5,000 to 20,000...

Embodiment 2

[0101] Screening of anticancer agents showing synergy in melanoma by combination therapy with gossypol and phenformin

[0102] In order to select a synergistic combination that can exhibit the anticancer effect of melanoma, in addition to gossypol and phenformin, vemurafenib (Vemurafenib, PLX032), cisplatin (cisplatin) and oxaliplatin (oxaliplatin) Each test drug was selected as a candidate anticancer agent.

[0103] Specifically, the UACC62 cell line or the A375 cell line were respectively cultured as melanoma cell lines, the same method as in [Example 1] was carried out, and whether the synergy of the anticancer effect was confirmed by SRB analysis through [Table 4] to [ Mixed administration of the anticancer agents disclosed in Table 6] was shown, and whether cell growth in melanoma cells was inhibited.

[0104] [Table 4]

[0105] The experimental design of the triple drug therapy group containing vemurafenib ( Figure 2A )

[0106]

[0107] [table 5]

[0108] The...

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Abstract

The present invention relates to a pharmaceutical composition comprising a combination of anticancer agents, capable of creating a synergistic effect when co-administered in the treatment of cancer, and more specifically, the present invention suggests anticancer agents capable of creating the synergistic effect when co-administered with gossypol and phenformin. The anticancer agents selected as anticancer agents in the present invention are sorafenib, vemurafenib, irinotecan, cisplatin, parclitaxel, and doxorubicin, and each of the aforementioned anticancer agents, when co-administered as a triple-drug combination with gossypol and phenformin, can provide a significant synergistic effect in terms of the effects of suppressing the proliferation of cancer and killing cancer cells, comparedto each mono-drug treatment group and a dual-drug treatment group of gossypol + phenformin.

Description

technical field [0001] The present invention relates to a pharmaceutical composition comprising a combination of anticancer agents capable of exhibiting a synergistic effect when administered in combination in cancer therapy, and more particularly, proposes a combination of gossypol and phenformin ) anticancer agents capable of exhibiting a synergistic effect when combined therapy. Background technique [0002] Cancer, unlike normal cells capable of proliferating and suppressing in a regular and restricted manner according to individual needs, is a cell mass composed of undifferentiated, infinitely proliferating cells that can ignore the necessary conditions in tissues, also known as tumors. Cancer cells with the ability to proliferate indefinitely can infiltrate surrounding tissue and, in more severe cases, metastasize to other organs in the body, causing severe pain and eventual death. [0003] Cancers are mainly divided into blood cancers and solid cancers, and can occur...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/11A61K31/155A61K31/44A61K31/437A61K45/06A61P35/00
CPCA61P35/00A61K31/11A61K31/155A61K33/243A61K31/4745A61K31/704A61K31/337A61K31/437A61K31/44A61P35/04A61K45/06A61K2300/00
Inventor 金铢烈朴种培李澔张铉
Owner 国立がんセンター
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