Preparation of polyphenol substance with anti-cancer effect
By standardizing polyphenol substance preparations and using the synergistic effect of natural substances such as curcumin, the problems of large and poor side effects of existing cancer treatment methods have been solved, and efficient treatment and minimized side effects of various cancers have been achieved.
Patent Information
- Application Number
- CN202380082223.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-09-26
- Publication Date
- 2025-07-04
AI Technical Summary
The existing cancer treatment methods have great side effects, strong toxicity to healthy cytokinesis, and limited targeted treatment effects. It is difficult to effectively eliminate all cancer cells, especially in advanced cancers.
Standardized polyphenol substance preparations are used, composed of natural substances such as curcumin, oleurin, EGCG, resveratrol, etc., and selectively produces cytotoxicity to tumor cells by synergistically affecting multiple cellular pathways, supporting the effectiveness of standard treatments and reducing side effects.
It enhances the effectiveness of cancer treatment, reduces side effects, selectively kills cancer cells, and reduces healthy cytotoxicity. It is suitable for a variety of cancer types, including breast, lung, prostate and colon cancer.
Smart Images
Figure BDA0005424247810000051 
Figure BDA0005424247810000061 
Figure HDA0005424247820000011
Abstract
Description
Technical Field
[0001] The present invention relates to a standardized polyphenol formulation which has an anti-cancer effect; and due to its antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, neuroprotective and systemic effects, it can selectively produce cytotoxicity to tumor cells, thereby supporting the effectiveness of standard treatment, and when used at the recommended dose, it has minimal side effects compared to drugs with anti-cancer, antioxidant and anti-inflammatory properties in the prior art. The mentioned formulation consists of a combination comprising at least one of the natural substances including: curcumin derived from plants, oleuropein, epigallocatechin gallate (EGCG), resveratrol, rosmarinic acid, carnosic acid and phenethyl caffeate (CAPE), apigenin, galangin, chrysin, luteolin, quercetin and pinocembrin, and these natural substances are present in both plants and propolis. Background Art
[0002] Cancer is a multifactorial disease that occurs due to the accumulation of various mutations in many different cellular pathways in normal tissues and the uncontrolled increase of abnormal cells. Cancer cells are cells that have acquired various characteristics to evade cellular control mechanisms, spread to adjacent or distant tissues and thus cause uncontrolled growth. These cells develop mechanisms to ensure their continuity through many different cellular pathways. For example, breast cancer cells exhibit different metabolic phenotypes depending on their molecular subtypes and metastatic sites. Both intrinsic factors (such as MYC amplification, PIK3CA and TP53 mutations) and extrinsic factors (such as hypoxia, oxidative stress and acidosis) play roles in different metabolic reprogramming phenotypes of metastatic breast cancer. Cancer cells divide uncontrollably and irregularly, accumulate and form tumor masses, and metastasize to surrounding tissues or distant regions by detaching from these cells and spreading into the vascular access or body cavity. This situation seems to be the most important obstacle to reducing the success rate of cancer treatment.
[0003] Cancer treatment varies depending on the patient and the type of cancer. The most common treatments are a combination of surgery, chemotherapy, and radiotherapy. However, surgery may not be able to remove all cancer cells. Additionally, since cancer cells have the potential to spread to different tissues, a single surgical intervention is not sufficient to eliminate all cancer cells. Radiotherapy, another treatment option often used in combination with surgery and chemotherapy, can have severe side effects on blood cells and surrounding tissues. In recent years, targeted immunotherapy and hormone therapy have become available based on the characteristics of the tumor. However, the lack of specific targeted treatment methods for certain types of cancer and the high treatment resistance rates observed in some targeted therapies limit the use and effectiveness of such treatments. For example, the effectiveness of monoclonal HER2 (human epidermal growth factor receptor 2) antibody treatment for HER2(+)(human epidermal growth factor receptor 2(+)) breast cancer cases varies by 30%-60% within the group. In the remaining cases, success is not achieved due to resistance mechanisms or side effects. In addition to all of these, immunotherapy and hormone therapy (as targeted therapies) can only be used when specific markers are found in cancer cells, which also limits the application of these treatment methods.
[0004] Another method used in cancer treatment is chemotherapy. More specifically, chemotherapy is the treatment of cancer using one or more anti-cancer drugs as part of a standard treatment regimen. The chemotherapeutic agents used in chemotherapy are drugs that kill cells by targeting various cellular mechanisms, preventing cell division, or causing DNA damage. However, these chemotherapeutic agents also have toxic effects on healthy cells. Due to these toxic effects, patients experience a high frequency of side effects, and patients may lose their lives due to chemotherapy alone and may even develop different types of cancer in the future. On the other hand, due to certain genetic characteristics, some patients may develop resistance to these agents, and they have to interrupt the treatment due to nausea, fatigue, and a decrease in blood values. Due to these limitations and / or adverse effects, new treatment methods are needed to support existing treatment methods without any side effects.
[0005] In the prior art, there have been many studies on treatment methods that support cancer treatment methods without side effects. Most of these methods include studies on breast cancer (one of the most common cancer types in women). Breast cancer is divided into multiple subtypes, and its mortality rate ranks second only to lung cancer. This fact has prompted most studies to focus on breast cancer. Therefore, there has been an increasing number of studies on natural and synthetic substances that can have chemotherapeutic effects in the treatment of breast cancer, as well as lung cancer, prostate cancer, colon cancer, and cancers of other organs. In the literature in this field, many studies have occupied a place, especially those involving compounds and derivatives obtained from plants and used in cancer treatment. However, since the compounds and their derivatives mentioned are usually studied using single or binary combinations, their mechanism of action has not been fully proven, and only limited gene relationships have been studied.
[0006] Surgical intervention, chemotherapy, radiotherapy, or combinations of these applications (all included in the standard cancer treatment methods in the prior art) may not be sufficient to minimize harm while treating cancer, and can only succeed in very few anecdotal cases (especially in metastatic cancers). In short, the treatment methods and combinations available in the prior art are insufficient in themselves, especially in treating advanced cancers and eliminating all cancer cells. In addition, these mandatory treatments have toxic effects on other healthy cells and organs, may cause side effects, and may even lead to the death of the patient. Immunotherapy and hormone therapy, as targeted therapies, are only effective to a limited extent against cancer cells carrying special markers. Besides all of these, in the prior art, although efforts are being made to develop formulations that have no side effects on cancer or breast cancer, these formulations are insufficient in terms of having no side effects, supporting standard treatment, and increasing treatment effectiveness.
[0007] Due to the limitations and deficiencies of cancer treatment applications in the prior art and the following facts: for example, applications such as surgical intervention, chemotherapy, radiotherapy, immunotherapy, and hormone therapy alone are not sufficient to treat cancer, these applications cause additional damage to the body and may even lead to the death of the patient in some cases, and they do not have the effectiveness to minimize the toxic effects in cancer treatment, it is necessary to develop a formulation that supports the treatment applications in the prior art, even improves the effectiveness of these applications, reduces their side effects, and has anti-cancer properties and minimizes side effects. Summary of the Invention
[0008] The present invention explains a standardized polyphenolic substance formulation with anti-cancer effects. Through its antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, neuroprotective and systemic effects, this standardized polyphenolic substance formulation can selectively produce cytotoxicity to tumor cells, thus supporting the effectiveness of standard treatment. And when used at the recommended dose, compared with the drugs with anti-cancer, antioxidant and anti-inflammatory properties in the prior art, it has minimal side effects. The mentioned formulation consists of a combination containing at least one of the natural substances including: curcumin derived from plants, oleuropein, epigallocatechin gallate (EGCG), resveratrol, rosmarinic acid, carnosic acid and phenethyl caffeate (CAPE), apigenin, galangin, chrysin, luteolin, quercetin and pinocembrin, and these natural substances exist in both various plants and propolis.
[0009] One of the objectives of the present invention is to provide a formulation that has anti-cancer effects, supports standard treatment, increases the effectiveness of standard treatment, and when used at the recommended dose, compared with the drugs with anti-cancer, antioxidant and anti-inflammatory properties, etc. in the prior art, has minimal side effects. In the present invention, a formulation with the mentioned properties is provided by ensuring that the formulation contains at least one or more of the following in a specific ratio: apigenin, galangin, phenethyl caffeate (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, rosmarinic acid, carnosic acid and pinocembrin. The given ingredients are obtained entirely from natural sources and consist of nutritional grade and / or pharmaceutical grade raw materials. These polyphenolic substances (which are already contained in human daily nutrition in a certain amount) have no obvious or significant side effects within a certain dose range. The formulation of the present invention is prepared by a multi-substance method at a relatively low dose, and by simultaneously affecting different cellular pathways, it prevents the tendency of cancer cells, which is often encountered, to turn to alternative pathways, thus having a harmful effect on the survival of cancer cells. In other words, through the formulation of the present invention, it is prevented that carbon is assimilated into macromolecules due to the carcinogenic signal transduction pathway guiding nutrient absorption, thus preventing the growth and proliferation of cancer cells.
[0010] Another objective of the present invention is to provide a standardized polyphenolic substance formulation with a high level of anti-cancer effects. A formulation with a high level of anti-cancer effects is provided by ensuring that the formulation contains at least one or more of the following in a specific ratio: apigenin, galangin, phenethyl caffeate (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, rosmarinic acid, carnosic acid and pinocembrin. The high anti-cancer activity is achieved by using the formulation which is the subject of the present invention at a percentage determined according to the stage of cancer and the clinical condition of the patient.
[0011] Another object of the present invention is to provide a formulation that highly supports / increases the effectiveness of standard cancer treatment. A formulation that highly supports standard cancer treatment is provided by ensuring that the formulation that is the subject of the present invention contains at least one or more of the following in a specific ratio: apigenin, galangin, caffeic acid phenethyl ester (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, rosmarinic acid, carnosic acid, and pinocembrin. Although the formulation of the present invention shows an anti-cancer effect on breast cancer types, it has no significant cytotoxic effect on breast fibroepithelial cells used as a control, and thus has the ability to provide additional benefits to standard cancer treatment.
[0012] Another object of the present invention is to provide a formulation that reduces the excessive oxidative activity (which may be highly toxic to healthy tissues) that may occur in standard cancer treatment, thereby reducing the side effects of standard treatment. A formulation that reduces the side effects of standard treatment without reducing its anti-cancer effectiveness is provided by ensuring that the formulation that is the subject of the present invention contains at least one or more of the following in a specific ratio: apigenin, galangin, caffeic acid phenethyl ester (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, rosmarinic acid, carnosic acid, and pinocembrin. Description of the Drawings
[0013] Figure 1 . Graph showing the cytotoxic effect of the apigenin-chrysin-galangin formulation on the MCF-7 cell line
[0014] Figure 2 . Graph showing the cytotoxic effect of the apigenin-chrysin-galangin formulation on the MCF-10A cell line
[0015] Figure 3 . Graph showing the cytotoxic effect of the catechin formulation on MCF-7 cells
[0016] Figure 4 . Graph showing the cytotoxic effect of the catechin formulation on MCF-10A cells
[0017] Figure 5 . Graph showing the cytotoxic effect of the flavonoid formulation on the MCF-7 breast cancer cell line
[0018] Figure 6 . Graph showing the cytotoxic effect of the flavonoid formulation on the control MCF-10A cell line
[0019] Figure 7 . Cell cycle analysis of control MCF-7 cells
[0020] Figure 8 . Cell cycle analysis of MCF-7 cells treated with 10% flavonoid formulation at the 24th hour
[0021] Figure 9 . Cell cycle analysis of MCF-7 cells treated with 10% flavonoid formulation at the 48th hour
[0022] Figure 10 . Histogram of fold change in protein expression of aurora kinase A (AURKA) and aurora kinase B (AURKB) in MCF-7 cells treated with flavonoid formulation compared with the control
[0023] Figure 11 . Graph showing the dose-time dependent cytotoxic effect of flavonoid formulation on HER2(+) / SKBR-3 breast cancer cell line
[0024] Figure 12 . Graph showing the dose-time dependent cytotoxic effect of the polyphenol formulation of the present invention on HER2(+) / SKBR-3 breast cancer cell line
[0025] Figure 13 . Graph showing the dose-time dependent cytotoxic effect of the polyphenol formulation of the present invention on triple-negative / MDA-MB-231 cell line
[0026] Figure 14 . Graph showing the dose-time dependent cytotoxic effect of the polyphenol formulation of the present invention on fibrocystic MCF-10A mammary epithelial cell line
[0027] Figure 15 . Graph showing the dose-time dependent cytotoxic effect of the polyphenol formulation of the present invention on ER(+) / PR(+) MCF-7 breast cancer cell line
[0028] Figure 16 . Inverted light microscope image showing the effect of the polyphenol formulation of the present invention on cell migration of MDA-MB-231 cell line
[0029] Figure 17 . Comparison of the effect of the polyphenol formulation of the present invention on human peripheral blood mononuclear cells (PBMC) and its effectiveness against mitogenic stimulant (PHA) Detailed Description of the Invention
[0030] The present invention relates to a standardized polyphenol formulation which has an anti-cancer effect; in particular, through its antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, neuroprotective and systemic effects, it can selectively exert cytotoxicity on tumor cells, thereby supporting the effectiveness of standard treatment; and when used at the recommended dose, it has minimal side effects compared to drugs with anti-cancer, antioxidant and anti-inflammatory properties in the prior art. The mentioned formulation consists of a combination comprising at least one of the natural substances including: curcumin derived from plants, oleuropein, epigallocatechin gallate (EGCG), resveratrol, rosmarinic acid, carnosic acid and phenethyl caffeate (CAPE), apigenin, galangin, chrysin, luteolin, quercetin and pinocembrin, and these natural substances exist in both plants and propolis. The content of the active polyphenol substances in the formulation which is the subject of the present invention varies according to the type and stage of the cancer for which the formulation will be used. The formulation which is the subject of the present invention is prepared in the form of a suspension, syrup, sachet, tablet or capsule, and in addition to the active ingredient, also contains excipients in an appropriate proportion such as dextrose, maltose, maltodextrin or β-cyclodextrin, etc.
[0031] The content of the active polyphenol substances in the formulation which is the subject of the present invention varies according to the type and stage of the cancer for which the formulation will be used. The formulation which is the subject of the present invention is prepared in the form of a suspension, syrup, sachet, tablet or capsule, and in addition to the active ingredient, also contains excipients in an appropriate proportion such as dextrose, maltose, maltodextrin or β-cyclodextrin, etc.
[0032] The polyphenol formulation which is the subject of the present invention has an anti-cancer effect, and kills cancer cells and provides an increase in immune system cells by synergistically affecting many genes involved in cell division, programmed cell death and many other pathways.
[0033] The polyphenol formulation of the present invention can be used to combat various cancers by changing the content ratio. The daily treatment dose should be a total phenolic content of 10 - 200 mg / kg / day, depending on the type and stage of the disease. Table 1 gives the ratio of the minimum and maximum percentages of polyphenols in the mixture (by mass).
[0034] Table 1. Ratio of the active ingredients contained in the polyphenol formulation which is the subject of the present invention
[0035]
[0036]
[0037] The content of the active polyphenolic substances in the formulations which are the subject of the present invention varies according to the type and stage of the cancer for which the formulation is to be used in the treatment. The formulations which are the subject of the present invention are prepared in the form of suspensions, syrups, sachets, tablets or capsules and contain, in addition to the active ingredient, excipients in appropriate proportions such as dextrose, maltose, maltodextrin or β-cyclodextrin.
[0038] In one embodiment of the present invention, the formulation according to the present invention comprises at least three of the following: apigenin, galangin, caffeic acid phenethyl ester (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, carnosic acid, rosmarinic acid and pinocembrin.
[0039] In one embodiment of the present invention, the formulation according to the present invention comprises at least four of the following: apigenin, galangin, caffeic acid phenethyl ester (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, carnosic acid, rosmarinic acid and pinocembrin. The formulation comprises apigenin, galangin, chrysin and oleuropein.
[0040] Figures 1 - 17 The activity of the polyphenol mixture of the present invention against cell lines representative of various types of breast cancer as an example disease group is shown.
[0041] Figure 1 is a graph showing the cytotoxic effect of the apigenin-chrysin-galangin formulation on the MCF-7 cell line, Figure 2 is a graph showing the cytotoxic effect of the apigenin-chrysin-galangin formulation on the MCF-10A cell line. The combined effect of some flavonoids on the MCF-7 cell line (a model of invasive ductal ER / PR(+) breast cancer (the most common type of breast cancer)) and the MCF-10A cell line (a model of fibrocystic breast epithelium, as a control) was examined. Starting from a low dose (15 μg / mL) and continuing up to the highest dose, especially at 48 hours, a significant cytotoxic effect of the apigenin-chrysin-galangin formulation on MCF-7 cells was detected, and this effect was confirmed to be an apoptotic effect by Annexin FITC assay. No cytotoxic effect of this formulation on the control MCF-10A cells, thus reducing cell viability, was detected.
[0042] Figure 3 shows a graph showing the cytotoxic effect of the catechin formulation on MCF-7 cells, Figure 4The cytotoxic effect of the catechin formulation on MCF-10A cells is shown. A similar effect to the apigenin-chrysin-galangin formulation was detected for the prepared flavanol (catechin) formulation in MCF-7 breast cancer cells, and the cytotoxic effect of the catechin formulation increased continuously from a very low dose (25 μg / mL) to the highest dose (in 50% of the cells), especially at the 48th hour, and this effect was confirmed to be due to apoptosis by the Annexin VI assay. In the cytotoxicity experiment, statistically significant results were obtained starting from the dose of 100 μg / mL at the 24th hour and the dose of 50 μg / mL at the 72nd hour. Similar to the apigenin-chrysin-galangin formulation, no cytotoxic effect of the catechin formulation on MCF-10A cells was observed.
[0043] Figure 5 is a graph showing the cytotoxic effect of the flavonoid formulation on the MCF-7 breast cancer cell line, Figure 6 is a graph showing the cytotoxic effect of the flavonoid formulation on the control MCF-10A cell line. A significant effect of the flavonoid formulation on cell viability / cytotoxicity was observed in the MCF-7 breast cancer cell line. At the early and late stages (24th, 48th, and 72nd hours), the flavonoid formulation caused a significant decrease in the cell viability of MCF-7 cells at a dose of 35% (although statistically significant). Additionally, no cytotoxic effect of the flavonoid formulation on the fibrocytic breast epithelial MCF-10A cells used as a control was observed at any time and dose, as Figure 6 shown.
[0044] Figure 7 shows the cell cycle analysis of the control group MCF-7 cells, Figure 8 shows the 24-hour cell cycle analysis of MCF-7 cells treated with 10% flavonoid formulation, Figure 9 shows the 48-hour cell cycle analysis of MCF-7 cells treated with 10% flavonoid formulation. In the cell cycle analysis performed, it was observed that 70% of the cells in the MCF-7 cell line without the application of the flavonoid formulation were in the G2 / M phase, in other words, they were in the active division phase, and by applying a 10% dose of the flavonoid formulation to MCF-7 cells, it was observed that the MCF-7 cells were arrested in the S phase within the first 24 hours, and at the 48th hour, the vast majority of the surviving cells were arrested in the G0 / G1 phase. In other words, the polyphenol formulation of the present invention inhibits the proliferation of cancer cells.
[0045] Figure 10A histogram showing the fold change in the expression of aurora kinase A (AURKA) and B (AURKB) proteins in MCF-7 cells treated with a flavonoid formulation compared to the control is presented. A significant decrease in the expression of both aurora kinase A and aurora kinase B was detected in MCF-7 cells treated with the flavonoid formulation. Aurora kinases are mitotic kinases that are highly expressed in most cancers and are responsible for regulating many events, including centrosome maturation, entry into mitosis, centrosome separation, bipolar spindle assembly, metaphase chromosome alignment, and cytokinesis. Therefore, the expression of these two enzymes at the protein level was analyzed using "western blotting", and it was confirmed that the expression of both proteins was significantly reduced. In other words, the formulation of the present invention reduces the expression of aurora kinase A and B proteins and shows an inhibitory effect on cell division.
[0046] The dose-time dependent cytotoxic effect of the progressive flavonoid formulation study on HER2(+)(human epidermal growth factor receptor 2(+)) breast cancer cell lines is shown in Figure 11 as follows. From Figure 11 the figures in it, it can be clearly seen that the mentioned flavonoid formulation is not effective enough for SKBR-3 cells (a model of more aggressive HER2(+) breast cancer, the incidence of which is increasing in society), so the effectiveness is achieved by enriching the formulation.
[0047] As a result of all these reasons explained and supported by the figures, the polyphenol formulation that is the subject of the present invention provides a formulation that may be effective in MDA-MB-231 cell lines (a model of triple-negative (ER / PR(-) and HER2(-)) type of breast cancer that is more resistant to chemotherapy and has a higher recurrence rate) and SKBR3 cell lines (a model of HER2(+)(ER / PR(-) and HER2(+)) type) and in adenocarcinomas of other tissues. Based on the findings obtained from the cytotoxicity analysis, it has been determined that the formulation that is the subject of the present invention is also effective in invasive types of breast cancer. The mentioned activities can be clearly understood from the figures in Figure 12 and Figure 13 the figures in Figure 12 which shows the dose-time dependent cytotoxic effect of the polyphenol formulation of the present invention on the HER2(+) / SKBR-3 breast cancer cell line, Figure 13 and the figure in
[0048] Figure 14 A figure showing the dose-time dependent cytotoxic effect of the polyphenol formulation of the present invention on the fibro-cystic MCF-10A mammary epithelial cell line is given, Figure 15Figure showing the dose-time dependent cytotoxic effect of the polyphenolic formulation of the present invention on the ER(+) / PR(+) MCF-7 breast cancer cell line. Starting from low doses and early stages, the cytotoxic effect of the polyphenolic formulation which is the subject of the present invention on the ER(+) / PR(+) MCF-7 breast cancer cell line was determined, which was confirmed by Annexin V to be induced by apoptosis. The cytotoxic effect of the polyphenolic formulation of the present invention on MCF-10A control cells was also observed. As we previously described, MCF-10A cells are non-tumorigenic fibro-cystic breast epithelial cells. All these results indicate that the polyphenolic formulation of the present invention is effective not only against hormone-positive and hormone-negative breast cancers, but also against fibro-cystic changes in breast tissue.
[0049] Therefore, the evaluation of the effects of the polyphenolic formulation which is the subject of the present invention observed at different stages in different cell lines by cell cycle analysis shows that the mentioned formulation is effective at different points in the cell cycle, and PCR array analysis shows that the formulation which is the subject of the present invention is effective on many pathways related to cell cycle arrest (especially in the G0 / G1 phase) and apoptosis induction. The given results were obtained by counting apoptotic, necrotic and live cells in "cell cycle analysis" and by apoptosis analysis using Annexin V-propidium iodide on a flow cytometer device. Additionally, when the effect of the polyphenolic formulation of the present invention on cell migration was examined in a scratch test of metastatic and hormone-negative MDA-MB-231 cells, it was found that the formulation of the present invention has a dose-dependent reducing effect on cell migration. Since cell migration establishes an experimental metastasis model, a reduction in migration indicates a decrease in the metastatic properties of the cells. It has been determined and proven that a 35% dose of the formulation which is the subject of the present invention inhibits cell migration until the 48th hour and has a cytotoxic effect on all cells at the 48th hour. Figure 16 Image showing the effect of the polyphenolic formulation of the present invention on the cell migration of the MDA-MB-231 cell line, taken under an inverted optical microscope.
[0050] It has been determined that the polyphenolic formulation of the present invention increases the persistence and viability of human peripheral blood mononuclear cells (PBMCs) and inhibits the increase of immune system cells due to external stimuli (phytohemagglutinin (PHA)). This shows that the formulation of the present invention also enhances the immune system in a controllable manner. These effects are clearly seen from Figure 17 the figure which compares the effect of the polyphenolic formulation of the present invention on human peripheral blood mononuclear cells (PBMCs) and its effectiveness against the mitogenic stimulant (PHA).
[0051] Briefly, the fact that the ingredients mentioned in the present invention are combined in specific proportions makes the formulation of the present invention have a synergistic effect effective against cancer. The formulation of the present invention is effective against MDA-MB-231 and SKBR3 cell lines, which are models of breast cancer types that are more resistant to chemotherapy and have a higher recurrence rate. Additionally, the polyphenol formulation is also effective in invasive types of breast cancer. In addition to all of these, the mentioned formulation has a cytotoxic effect on MCF-7 breast cancer cell lines at low doses and early, and also has a cytotoxic effect on fibro-cystic MCF-10A cells used as a control. The polyphenol formulation of the present invention increases the persistence and survival rate of human peripheral blood mononuclear cells (PBMC), and inhibits the increase of immune system cells caused by external stimuli (phytohemagglutinin (PHA)). Therefore, the formulation of the present invention also enhances the immune system in a controllable manner. The formulation of the present invention is effective against various adenocarcinomas (such as respiratory system cancer, digestive system cancer, and urogenital system cancer, etc.) that undergo similar carcinogenic pathways and show similar gene expression, especially breast cancer.
Claims
1. An anti-cancer polyphenol formulation, which comprises at least one of the following: apigenin, galangin, caffeic acid phenethyl ester (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, carnosic acid, rosmarinic acid, and pinocembrin.
2. The formulation according to claim 1, which comprises at least one of the following by mass: 1%-10% apigenin, 1%-10% galangin, 1%-10% caffeic acid phenethyl ester (CAPE), 1%-10% chrysin, 1%-10% curcumin, 1%-10% epigallocatechin gallate (EGCG), 1%-10% luteolin, 1%-10% oleuropein, 1%-10% quercetin, 1%-10% resveratrol, 1%-10% carnosic acid, 1%-10% rosmarinic acid, and 1%-10% pinocembrin.
3. The formulation according to claim 1 or 2, which comprises at least three of the following: apigenin, galangin, caffeic acid phenethyl ester (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, carnosic acid, rosmarinic acid, and pinocembrin.
4. The formulation according to claim 1 or 2, which comprises at least four of the following: apigenin, galangin, caffeic acid phenethyl ester (CAPE), chrysin, curcumin, epigallocatechin gallate (EGCG), luteolin, oleuropein, quercetin, resveratrol, carnosic acid, rosmarinic acid, and pinocembrin.
5. The formulation according to claim 4, which comprises apigenin, galangin, chrysin, and oleuropein.
6. The formulation according to claims 1-5, wherein the formulation is in the form of a suspension, syrup, sachet, tablet, or capsule.
7. The formulation according to claim 6, which comprises by mass 1%-10% apigenin, 1%-10% galangin, 1%-10% caffeic acid phenethyl ester (CAPE), 1%-10% chrysin, 1%-10% curcumin, 1%-10% epigallocatechin gallate (EGCG), 1%-10% luteolin, 1%-10% oleuropein, 1%-10% quercetin, 1%-10% resveratrol, 1%-10% carnosic acid, 1%-10% rosmarinic acid, and / or 1%-10% pinocembrin.
8. The formulation according to claim 1 or 7, wherein the daily therapeutic dose is 10-200 mg / kg / day.