TW201132342A - Antrocin containing pharmaceutical compositions for inhibiting cancer cells - Google Patents

Abstract

This subject invention is directed to a pharmaceutical composition for the inhibition of cancer cells, comprising an effective amount of a compound of formula I (Sesquiterpene lactones, antrocin) or pharmaceutical acceptable salts thereof, together with a pharmaceutically acceptable carrier.

Description

201132342 VI. Description of the Invention: [Technical Field of the Invention] The present invention relates to a pharmaceutical composition containing a compound of the formula I, which is useful for inhibiting the growth of cancer cells. [Prior Art] Cancer can be regarded as a malignant (10) tumor, a kind of _. It is characterized by an abnormal mass of malignant tissue resulting from excessive cell division. Cancer cells do not have the limits of normal cell growth and can invade and occupy the range normally reserved for other cells. The types of cancer treatment include chemotherapy, surgery, radiation, and a combination of these treatments. Chemotherapy usually involves the use of one compound that inhibits the growth of cancer cells. _ Many cancer chemotherapy regimens have been developed so far, but more effective chemotherapy is still needed. SUMMARY OF THE INVENTION The present invention is based on the discovery that the compound of formula I - Andrews or a pharmaceutically acceptable salt thereof, can be used to inhibit cancer cell growth 'even treatment or lion cancer, _ is breast cancer. In particular, the present invention provides a pharmaceutical composition for inhibiting cell growth, or even treating or lion cancer, comprising an effective amount of a compound of formula I, Android, or it can be green, and (iv) acceptable. The present invention provides a pharmaceutical composition which inhibits the growth of cancer cells, and has been experimentally confirmed to be a compound of the formula I-Android for different cancer cell lines (including: colorectal cancer cells _HT_29 or HCT116; Lai Xilin _Huh7; Weng cancer 杂 Α Α 及 及 及 及 及 及 及 及 MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD MD A comparative experiment with the clinical chemotherapy of cancer, Leucomycin D〇X〇mbicin and Cisplatin, to evaluate the relative inhibitory effect of compound-Android, oxytetracycline, and lysine on malignant breast cancer cells _ Α 加 ' Confirmed that under the _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ Can have - or more The palm center, therefore, has various stereoisomeric forms. The formulae mentioned in the present invention include all such isomers. The compound of formula j has the effect of selectively inhibiting cell growth. Because of its extremely small molecular weight, The therapeutic formula can be obtained by using a lower dose of the compound and the medicinally acceptable green, and the medical red is acceptable, and the desired therapeutic effect can be obtained. The present invention is a pharmaceutical composition for inhibiting cancer cell growth and even treating or preventing cancer. The substance is an effective amount of a compound of the formula I and a pharmaceutically acceptable salt thereof, which inhibits cancer cells or is administered to a patient in need thereof (the patient has cancer, symptoms of cancer or a constitution that is prone to cancer). The purpose of healing, restoring, alleviating, mitigating, altering, treating, ameliorating, improving, or affecting a disease, a symptom of a disease, or a constitution that is prone to disease. The term "an effective amount" as used herein refers to an effective amount. Compound - Andrew, and its pharmaceutically acceptable salt, has an amount of inhibitory or therapeutic effect. The effective amount of the change is based on the route of the music and the excipient usage. And co-usage active agents. Cancer herein means cell tumors. Cancer cells have the ability to grow aut〇nomous, ie rapidly proliferate cells under abnormal conditions or conditions. The cancer referred to herein includes all types of cells of cancer growth or oncogenic processes, metastatic tissue or malignant transformation of cells, tissues or organs (not related to histopathology) or invasion. Stages. Examples of cancer include, but are not limited to, cancer and sarcoma, such as breast cancer, leukemia, sarcoma, lymphomas, malignant osteosarcoma. (osteosarcoma), glioma, pheochromocytoma, hepatoma, 201132342 melanoma ovarian cancer, skin cancer, colorectal Cancer), gastric cancer, pancreatic cancer, renal cancer, prostate cancer, prostate cancer (testicular cancer)' Head and neck cancer, brain cancer, esophageal cancer, bladder cancer, adrenal cortical cancer, lung cancer , bronchus cancer, endometrial cancer, nasopharyngeal cancer, cervical, liver cancer (cervical or iiver canCer) or cancer at an unknown starting position. The compound of the formula I-Android is extracted by extracting the growing A. angustifolia (a fungus) from the burdock wood by an organic solvent and is prepared by separation and purification from the Shixi rubber column; or by chemical synthesis. For example, the extract of Antrodia camphorata, which is extracted from the growth and growth of burdock, refers to the extract of Antrodia camphorata extracted from the more suitable growth degree of Antrodia camphorata. To obtain the extract of Antrodia camphorata, extraction techniques well known in the art can be used. For example, the dried and ground Astragalus sinensis may be suspended in a solvent or a mixture of two or more solvents for a sufficient period of time. Examples of suitable solvents include 'but are not limited to · water, methanol, ethanol, dichloro Aromatic chloroform, acetone, ether (such as diethyl ether) and ethyl acetate and hexane (hexane). After removing the solid residue (for example, by φ filtering), the extract of the extract of Antrodia camphorata can be obtained by purifying the compound of the formula I by the Shixi rubber column - Andrew. Fortunately, nearly twenty years in the world. In the study of natural compounds contained in Antrodia camphorata, in addition to macromolecules such as polysaccharides, a total of seventy-eight small molecule compounds, including three-one diterpenoids, have been published and are mostly related. The study of physiological activity, especially focusing on these anticancer activities, only the individual molecules of diterpenoids must be used at higher levels to achieve the effect of cancer clinical chemotherapeutic drugs [Geethangili M and Tzeng YM, Review of pharmacological Effects of Antrodia camphorata and its bioactive compounds. Evidence-based Complementary and Alternative Medicine, published online on Aug. 17, 2009; doi: 10.1093/ecam/nepl08]. However, the compound of formula I - Andrew was for the first time reported in 1995 After being discovered in Antrodia camphor [Chiang HC, Wu DP, Chemg IW, Ueng CH. A sesquiterpene 201132342 lactone, phenyl and biphenyl compounds from Antrodia cinnamomea e-shoulder; 39:613 rhyme] 'So far, there has been no correlation for fifteen years Reported that its pharmacological activity report is also lacking. The Lai is a compound of the formula I. Andrew is fortunate to have a relatively low age and easy to isolate, and the invention is in the specific growth of shouting cows. Can be obtained by extraction, separation and purification. _, the present invention found that the compound Andrew fortuned to different cancer cell lines (including : Colorectal cancer cells grab 29 $ HCT116; liver cancer cell line - Huh7, lung adenocarcinoma cell line Α 549 and breast cancer cell line _] ^ (:: 177 or highly inhibitory, but for normal cells (including: _ mother cells _脳8 and normal mammary epithelial cells-MCF10A) are almost non-cytotoxic; in addition, a compound of formula I is evaluated by a clinical trial with cancer clinical chemotherapeutic drugs (Doxorubicin and Cisplatin). The relative inhibitory effect of oxytetracycline and cisplatin on malignant breast cancer cells (MDA-MB-231). It was confirmed that the compound of formula I-Android successfully inhibited malignant breast cancer cells at the same dose, which was superior to that of dexamethasone Doxorubicin. It started with Cisplatin, so it can even be used to treat and/or prevent cancer. It must be emphasized here: the formula _Android _ is the natural compound contained in the burdock, the only experimentally confirmed inhibition of cancer cells compared to the cancer clinical chemotherapeutic drugs (Doxorubicin and Cisplatin) The natural compound contained in Antrodia camphorata. In the method of the present invention, the compound of the formula I - Andrews or a pharmaceutically acceptable salt thereof, may be administered simultaneously or separately, orally, parenterally by inhalation spray (inhaiati〇n spray) or by The way to implant the reservoir (implantedreservoir). As used herein, "non-oral" refers to subcutaneous, intracutaneous, intravenous, intramuscular, intraarticular arteries (intrasynovial). , intrastemal intrathecal, intraleacial and intracranial injection and perfusion techniques. The compound of formula I used in the present invention - Andrews &/or a pharmaceutically acceptable salt thereof, may be combined with at least one solid, liquid or semi-liquid excipient or adjuvant to form a suitable pharmaceutical form. Forms thereof include, but are not limited to, 'medicine tablets, capsules, emulsions, aqueous suspensions (aqueous 201132342 sus_i〇ns), dispersions and solutions. The carrier (4) η (4) generally used for the drug bond includes lactose and jade green powder. The Gubrieating agent, such as the town of stearic acid (magnesiumst_te), is added to the tablet. The diluent used in the form of a capsule (iv) this includes lactose and dried cornstarch. When administered orally as an aqueous suspension or emulsion, the active ingredient (active(4)(4) can be suspended or dissolved in an oil phase combined with an emulsifying or suspending agent (Kissing (4). If necessary, a specific sweetness, flavoring and coloring agent can be added. The present invention allows the compound I, the Android core, and the blush to be formulated into a sterile injectable component (e.g., a suspension of water or oil), for example, using techniques known in the art. Dispersing or enhancing agents (eg Tween® with suspending agents. Sterile injections can also be added to sterile injectable solutions or suspensions to non-toxic non-oral diluents or solvents such as hydrazine, 3,butanediol (1,3-Butanedi〇) l). Vehicles and solvents that can be used include mannitol, water, Ringer's soluti〇n and isotonic gasification nanosolutions. In addition, sterile and fixed oils are often used. Solvents or suspension media (for example, synthetic mono- or di-glycerides). Fatty acids, such as oleic acid and its glyceride derivatives, can also be used in the preparation of injectables, which are naturally pharmaceutically acceptable. Oils, such as olive oil, castor oil, especially in their polyoxyethylated (p〇ly〇Xyethy丨ated) variants. These oil solutions or suspensions may also contain a long An alcohol-based diluent or dispersant, or a carboxymethyl cellulose or a similar dispersing agent. The compound of the formula I used in the present invention - Andrew Xing or a pharmaceutically acceptable salt thereof may also be used in the technical field. The well-known technique is formulated into an inhalation component, for example, a salt solution, a benzyl alcohol or other suitable preservative, an adsorption enhancer for enhancing bioavailability, and a carbon I compound ( Fluorocarbon) or other solubilizing or dispersing agents well known in the art. The carrier for the pharmaceutical composition must be "acceptable" which is compatible with the active ingredients of the formulation (and preferably has a stable active ingredient) Ability) and not harmful to the patient. For example, solubilizing 201132342 (eg cyclodextrins) (which forms a more soluble form with the active compound of one or more extracts) Complex), as a pharmacological adjuvant for the delivery of active ingredients. Examples of other carriers include colloidal dioxide dance olloidalsilic〇ndi〇xide), stearic acid town, cellulose and sodium lauryl "In addition, because of the anti- _ _ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ ̄ Valid # is 0.0_ to _, preferably 〇·5μΜ to the piano. The treatment of a patient's narration #丨1: ritual may be determined at all times, such as the specific compositive sentence of the Κ Xiao, age, body weight, _ general health status, gender, eating status, off time and road excretion rate, medical The combination of music substances, and the severity of the disease to be treated. The above and other objects, features, and advantages of the present invention will become more apparent and understood <RTIgt; <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; The selected Antrodia camphorata was lyophilized, pulverized, and then subjected to hot reflux extraction with methanol, and then filtered to obtain a precipitate and a methanol extract. After the decyl alcohol extract is concentrated under reduced pressure into a sticky shape, the chloroform layer is added to an appropriate amount of yttrium gel and concentrated under reduced pressure to a powder, and then filled into the upper end of the ruthenium tube column to carry out the ruthenium tube column. Chromatography, purification to prepare a compound of formula I - Andrew Fortunate. Example 2: Biological activity analysis method: 1. Activation of cold bundle cells The activation principle of frozen cells is rapid thawing to avoid recrystallization of ice crystals and cause damage to cells, leading to cell death. After cell activation, it takes about a few days, or one to two generations, and its cell growth or characteristic performance will return to normal (for example, producing monoclonal antibodies or other proteins). The frozen cells are quickly thawed by removing the cryotube from the liquid nitrogen or dry ice container, immediately immersing them in a 37 C water bath, and gently shaking the cold tube to melt them in 3 minutes. The outside of the tube is moved into the aseptic table. The thawed cell suspension was taken out, and the medium was cultured in a medium (7) 2 incubator. In _^=day = medium. , 201132342 2. Culture of human breast cancer cells Three different human breast cancer cell lines were selected for this experiment: normal breast epithelial cells (MCF10A cells), human breast precancerous cells (MCF-7 cells), and human malignant breast cancer cells (MDA-MB). -231 cells). MDA-MB-231 cell line cultured in 5% fetal bovine serum (FBS), 2 mM glutamine '100 pg/ml streptomycin and 100 U/ml penicillin's Dulbecco's Modified Eagle's Medium (DMEM); MCF-7 cell line cultured in 5% fetal bovine serum, 2 mM glutamic acid, 100 pg/ml streptomycin and 100 U/ml penicillin, 0.01 mg/ml insulin (Dulbecco's Modified) In Eagle's Medium (DMEM); MCF10A cells were cultured in 5% horse serum (Horse Serum), skin epidermal growth factor (EGF) (final concentration 20 ng/ml), Hydrocorretisone (final concentration 〇.5) Mg/ml), Cholera Toxin (final concentration 100 ng/ml), insulin (final concentration lOpg/ml), 4 mM branic acid, 100 pg/ml streptomycin and 1〇〇xj/ml The above MDAMB231 and MCF7 cells in Dulbecco's Modified Eagle's Medium (DMEM) with penicillin and 0.01 mg/ml valerin were subcultured with 10% fetal bovine serum. The cell strain was placed in an incubator at 37 ° C, 5% CO 2 and 95% humidity. 3. Cell drug treatment: All the cells in the experiment were cultured in a culture medium containing 10% fetal bovine serum. When the cells were grown to about 80% full, the old culture solution was drained and used in PBS buffer (phosphate buffer). After washing the cells with the solution, add 10 ml of serum-free medium. Different drugs were added depending on the purpose of the experiment, and the reaction was carried out in a 37 ° C incubator. 201132342 4 :, cytotoxicity: Place malignant breast cancer cells (MDA-MB-231 cells), human breast precancerous cells (MCF-7 cells) and normal breast epithelial cells (MCF10A cells) in 96-well culture plates ( Culture plate) (2000 cells/well), and cultured overnight in 1 μμΐ of complete DMEM. 50 μΐ of a complete DMEM equivalent sample containing the compound of formula I - Andrews (0.5-10 μΜ) was added to the different wells of the plate. In addition, the control group only added 100 μΐ of complete DMEM. After 2 days of culture, the number of cells in each well was determined by analysis of sulforhodamine ( (protein binding dye). Briefly, cells were fixed in 10% trichloroacetic acid and stained with 0.4% sulforhodamine B. After staining for 20 minutes, it was washed with 1% acetic acid, after which the cell-bound sulforhodamine b was dissolved in 10 mM Tris base. The optical density was measured at 562 nm using a microtiter plate reader. The above method was also used to test the sensitivity of cells such as Huh7 hepatoma cells, A549 lung tumor cells, HT29 and HCT116 colorectal cancer cell lines to the compound of formula I. 5. Analysis of cell type changes There is a large difference in morphology between cell/apoptosis and necrosis, characterized by cell atrophy, shedding, and chromatin condensation. Place the malignant breast cancer cells (MDA-MB_231) in the culture medium, and then give the appropriate concentration of the drug containing the compound of formula I - Android (0.5-10 μΜ), in the incubator. After a period of time, the cell type was observed with an inverted microscope and photographed. 11 201132342 6. Cell cycle and apoptosis detection: Malignant breast cancer cells (MDAMB231) were treated with the compound of formula I - Andrews, and the cells were treated with trypto-ethylenediaminetetraacetic acid (trypSin-EDTA) and collected together with the culture solution. After centrifugation, the supernatant was removed and washed with 4 ° C phosphate buffer, and 1 ml of ice-cold 75% alcohol was added to the 40C refrigerator overnight to fix the cells. After centrifugation, continue! ML PBS was suspended by adding the appropriate amount of ribonucleic acid A_aseA at 37. (: For 30 minutes, finally add 40mg/ml propidium iodide (PI, Sigma Chemical Co., cat. No P-4170) for half an hour, with 35mm nylon mesh (four) 丨on mesh) After filtration, after excitation at a wavelength of 495 nm, the fluorescence content of the cells was detected at a wavelength of 637 nm, and analyzed by flow cytometry. Example 3 Results of Biological Activity Assay 1. The compound of Formula I - Andrew fortunes inhibits the growth of different tumor cells. Selection of different tumor cell lines including: colorectal cancer cell-HT-29 or HCT116; liver cancer cell line-Huh7; lung adenocarcinoma cell line-A549 and breast cancer cell line _MCF7 or MDAMB231 to explore the compound of formula I - Andrew fortunately for different cancers The poisoning effect of cells. It was found that the compound of formula I can significantly inhibit the growth of different tumor cells, and the semi-inhibitory concentration (IQo value) caused by the tumor cells is between 6.6~4·5μΜ, which is in the pair of malignant breast cancer cells (MDA- MB-231 cells) have the strongest poisoning effect (Figure 1). It is worth noting that further analysis is performed with fibroblasts (HS68) and normal mammary epithelial cells (MCF10A cells)! The effect of the compound on normal cell growth revealed that the compound of formula I did not cause growth inhibition in both normal cells (Fig. 2). From this, it was found that the compound of the formula I-Android has the ability to selectively kill cancer cells, and the poisoning effect of breast cancer is most remarkable. 12 201132342 2: Compound of formula I - Andrew fortuned with the chemotherapeutic drug erythromycin (D〇x〇rubidn) and cisplatin (Cisplatin) using the SRB method to compare the compound of formula I_Android, d〇x〇mbidn The utility of cisplatin with malignant breast cancer cells (MDA-MB-231 cells). Doxorubicin and cisplatin are one of the commonly used anti-breast cancer drugs on the market. d〇x〇rubidn mainly forms a complex with DNA in the organic salt-containing base of DNA, inhibits the activity of polymerized hydrazine, or is beneficial by production. The superoxide free root attack DNA can affect the synthesis of DNA in cancer cells; the action of cisplatin is mainly covalently bonded to the DNA of cancer cells, causing the interaction between the two strands of DNA to inhibit the DNA synthesis of tumor cells. After 48 hours of administration of the drug, it was found that doxorubicin was between 5 and 1 μ〇, maintaining 60-70% toxicity for malignant breast cancer cells (MDA-MB-231 cells), while the compound of formula j was at a concentration of 5 μΜ or more. It is higher than doxorubicin, and the cytotoxicity of 恶μΜ is higher than 3〇% eCisplatin for malignant (tetra) cells (MDA_MB_23leells) at the concentration of the control group, which is only 30% toxicity at 1〇μΜ (Fig. 3). 3. The compound of formula I - Andrew's effect on the growth of malignant breast cancer cells and normal breast epithelial cells. From the experimental results, it was found that the compound of the formula I - Andrew, did have a better inhibitory effect on breast cancer cells. Therefore, the malignant breast cancer cell cdls), human breast precancerous cells (MCF-7 cells) and normal breast epithelial cells (MCF1〇A ceUs) were further assayed by the method of Sulforfiodamine B (SRB assay) for the growth of cell growth. . The principle of SRB analysis is to use coloring agent (Suif〇rh〇damineB, SRB) to form a color with the basic amino acid bond of cytoplasmic protein, which is mainly used to measure the proliferation and survival rate of cells. The results showed that after 48 hours of administration of the drug, the malignant breast cancer cell line __231) and the human breast precancerous cell (MCF7) increased significantly with the increase of the concentration of the compound of formula I. 13 201132342 increased under the compound of formula I/agricultural ΙμΜ treatment It can inhibit the survival rate of brain secret cells (Table- and Table 2). The cell viability of normal mammary epithelial cells (mcf secret) did not affect the concentration of the compound of formula I (Table 3). Therefore, it can be known that the compound τ compound _ Android has a high cytotoxicity against MDAjVtBm and human dermal herpes (MCF7), but not too high cytotoxicity to normal breast epithelial cells (MCF1〇A). One is to analyze the cytotoxicity of the compound of formula I-Android for malignant breast cancer cells (MDAMB231) with SRB (3), and to evaluate the compound of formula I by SRB analysis - Andrew fortunately for malignant breast cancer cells Cytotoxicity of (MCF7). Table 3 shows the cytotoxicity of the compound of formula I by SRB analysis_Android for normal mammary epithelial cells (MCF1〇A). Table I's evaluation of formulae 丨 compound for malignant breast cancer cells (MDAMB231) by SRB analysis ) cytotoxic 丨 compound concentration _) absorbance relative cell viability (%) 0 0.484 ± 0.009 100 0.5 0.301 ± 0.004 62.1 1 0.103 ± 0.001 21.2 3 0.082 ± 0.001 17.1 5 0.057 ± 0.004 11.8 10 0.032 ± 0.006 6.6 Relative cells Survival rate (%) = (absorbance value of the compound treatment group) / (absorbance value of the control group) X 1〇〇201132342 Table 2. Evaluation of the compound of the formula I on the human breast precancerous cells (MCF7) by SRB analysis Cytotoxicity 1 compound concentration (&quot;M) absorbance versus cell viability (%) 0 0.192 ± 0.005 100 0.5 0.148 ± 0.002 77 1 0.114 ± 0.003 59.5 3 0.091 ± 0.006 47.7 5 0.068 ± 0.005 35.8 10 0.046 ± 0.001 24.1 Relative Cell viability (%) = (absorbance of the compound treatment group) / (absorbance of the control group) X 100

Table 3. Evaluation of cytotoxicity of compound of formula I against normal mammary epithelial cells (MCF10A) by SRB analysis (&quot;M) Absorbance versus cell viability (%) 0 2.352 ± 0.002 100 0.5 2.265 ± 0.001 97.3 1 2.194 ± 0.004 93.2 3 2.143 ± 0.008 91.1 5 2.067 ± 0.003 87.8 10 1.935 ± 0_004 82.2 Relative cell viability (%) = (absorbance of the compound treatment group) / (absorbance of the control group) X 100 15 201132342 4· The effect of the compound of formula i - Andrews on the cell type of malignant breast cancer cell line (10) VIII. The present invention is a compound of the formula I, and the cytotoxicity of malignant breast cancer cells is caused by cell growth. In terms of cell type, since the cell/weekly death activates many endogenous egg self-feeds, it can cause cytoskeletal disruption, cell shrinkage, and bubble on the cell membrane. Membrane blebbing), and there is a phenomenon of chr〇matin condensation. From the experimental results, it was clearly observed that when the compound of the formula j was administered to the malignant breast cancer cell line MDA-MB-231, there was a significant atrophy change in the cell type, and an apoptotic body was clearly observed. This is a significant difference in appearance compared to control group cells treated without the addition of the compound. In addition, many cells were observed to have detachment and were suspended in the culture medium (Fig. 4). 5. The compound of formula I - Andrew fortunately causes the analysis of the death of malignant breast cancer cells MDA-MB-231 cells and its effect on the cell cycle. Since the DNA of normal humans is a double set (2N), the DNA of apoptotic cells is broken. Small fragments, therefore, have lower staining stainability than normal G0/G1 phase cells. After staining with propidiumiodide (PI), flow cytometry analysis can 'appear apoptotic cells' to form sub G1. Peak. Therefore, the present invention further performs PI staining on malignant breast cancer cell line MDA-MB-231 cells. The effect of the compound of formula I on the cell cycle is analyzed by flow cytometry. From the experimental results, it was found that the compound of the formula I (ΙμΜ and 5 μΜ) slightly increased the ratio of G0/G1 after 48 hours of action. In contrast, as time and concentration increased, the proportion of subGl in the cells treated with the compound of formula I also increased significantly (Fig. 5). 0 16 201132342 [Simplified illustration] Figure - Evaluation of the compound of formula I by SRB analysis - Andrew is cytotoxic to different cancer cell lines including: colorectal cancer cell-HT-29 or HCT116; liver cancer cell line _Huh7; lung adenocarcinoma cell line _ VIII 549 and breast cancer cell line - MCF7 or MDAMB231. Figure 2. Cytotoxicity of normal compounds (including fibroblast-HS68 and normal mammary epithelial cells-MCF10A) by SRB analysis. Figure 3. Comparison of the compounds of Formula I with the SRB analysis. The drug treatments (Acetomycin Doxombicin and Female Cisplatin) evaluated the cytotoxicity against malignant breast cancer cells (MDAMB 23l). Figure 4. Compound of Formula I·Android for the cell type change of the breast cancer cell line (^^_咖_231). Figure 5. Compound of Formula I - Andrews has caused a change in the cell cycle of a malignant breast cancer cell line (△ Lake 31) and caused an increase in cells in the sub G phase. [Description of main component symbols] Cover #, ,,

17

Claims (1)

201132342 Qishen May patent scope: 1. A pharmaceutical composition for inhibiting the growth of cancer cells, including an effective amount of a compound compound - Android #(Sesquiterpene lactones, antrocin) Or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 2. The pharmaceutical composition according to the above-mentioned patent application, which can treat or prevent cancer. 3. The pharmaceutical composition according to claim 1, wherein the cancer cells include colorectal cancer cells-HT-29 or HCT116; liver cancer cell line _Huh7; lung adenocarcinoma cell line _A549 or breast cancer cell line-MCF7 Or MDAMB231. 4. The pharmaceutical composition according to claim 2, wherein the cancer comprises breast cancer, leukemia, sarcastic sarcoma (sarc〇ma), malignant osteosarcoma (〇ste〇sarc〇ma) lymph Lymphomas, melanoma, glioma, pheochromocytoma, hepat〇ma, ovarian cancer, skin cancer , testicular cancer, gastric cancer, pancreatic cancer, renal cancer, renal cancer, prostate cancer, colon cancer Cancer in the neck, brain cancer, esophageal cancer, bladder cancer, adrenal cortical cancer, lung cancer, bronchus cancer, intrauterine Endometrial cancer, nas〇phaiyngeal cancer, cervical, liver cancer or cancer at an unknown starting location. 201132342 5. According to the scope of the patent application, the pharmacy mentioned in the first paragraph of the patent. ^. H silk, its I compound _ Andrew Koss Oesquiterpene lactones, antrocin) is based on the ancient land, 々 &amp; The burdock I is obtained by purifying the shixi rubber column. 6. The pharmaceutical composition according to claim 1, wherein the safe and effective amount of the compound "Android" is Ο.ΟΙμΜ to 1〇〇〇μΜ. According to the sixth item of the patent application. The pharmaceutically acceptable composition, wherein the compound & android is safe and effective, preferably from 0.5 μΜ to 50 μΜ.