Bisbenzoxazole derivatives had anti-proliferative effect on Human Cancer Cells

Natural products have played major roles in drug discovery programs including development of anticancer agents. In our continuing efforts to identify and characterize antitumor agents from natural products, we found the extract of the root of Cynanchum paniculatum (Asclepiadaceae) exhibited potent anti-proliferative effects in cultured human cancer cells. Bioassay-guided fractionation further led to the isolation of the bioactive constituent and was elucidated as antofine, a phenanthroindolizidine alkaloid. Antofine markedly inhibited the growth of several human cancer cells with the IC50 values in the nanomolar range. In view of the potential anti-proliferative effects against cancer cells we developed the procedure of total synthesis of antofine and further investigated the anti-proliferative mechanisms and antitumor effects. In HCT 116 human colon cancer cells, the plausible anti-proliferative mechanisms of antofine might be associated with the down-regulation of cyclin D1, cyclin E, and CDK4 expression, the inhibition of DNA synthesis, the modulation of Wnt signaling activation, and the induction of differentiation. Antofine also exhibited the potential growth inhibition of paclitaxel-resistant human lung cancer cells (A549-PA) along with the down-regulation of P-glycoprotein expression. Antofine also effectively suppressed tumor growth in the tumor xenograft model. In addition, daphnane-type diterpenoids were isolated from the flower of Daphne genkwa (Thymelaceae) with a potential anti-proliferative activity against human lung cancer cells. Yuanhuadine, one of the most potent isolates from D. genkwa, showed potent growth inhibition and a relatively strong selectivity against human lung cancer cells compared to a panel of several cancer cell lines. In A549 human lung cancer cells, yuanhuadine induced cell cycle arrest at either G0/G1 or G2/M phase depending on incubation time. The cell cycle arrest was well correlated with the expression of checkpoint proteins including the upregulation of cyclin-dependent kinase inhibitor p21, and down-regulation of cyclin B1, cyclin dependent kinases and c-myc. Yuanhuadine also inhibited the phosphorylation of Akt, the mammalian target of rapamycin (mTOR) and its downstream effector molecules, p70 S6 kinase 1 and eukaryotic initiation factor 4E binding protein 1, indicating that the induction of cell cycle arrest by yuanhuadine might be in part mediated by the suppression of Akt/mTOR signaling pathway. Taken together, these findings suggest that antofine and yuanhuadine might provide potential lead candidates for the development of cancer chemotherapeutic agents derived from natural products.

Sphingolipids such as ceramides (Cers) play important roles in cell proliferation, apoptosis, and cell cycle regulation. An increased Cer level is linked to the cytotoxic effects of several chemotherapeutics. Various selective cyclooxygenase-2 (COX-2) inhibitors induce anti-proliferative effects in tumor cells. We addressed the possible interaction of the selective COX-2 inhibitors, coxibs, with the sphingolipid pathway as an explanation of their anti-proliferative effects. Sphingolipids were measured using liquid chromatography tandem mass spectrometry. Treatment of various cancer cell lines with celecoxib significantly increased sphinganine, C(16:0)-, C(24:0)-, C(24:1)-dihydroceramide (dhCer) and led to a depletion of C(24:0)-, C(24:1)-Cer in a time- and concentration-dependent manner, whereas other coxibs had no effect. Using (13)C,(15)N-labeled l-serine, we demonstrated that the augmented dhCers after celecoxib treatment originate from de novo synthesis. Celecoxib inhibited the dihydroceramide desaturase (DEGS) in vivo with an IC(50) of 78.9 +/- 1.5 muM and increased total Cer level about 2-fold, indicating an activation of sphingolipid biosynthesis. Interestingly, inhibition of the sphingolipid biosynthesis by specific inhibitors of l-serine palmitoyltransferase diminished the anti-proliferative potency of celecoxib. In conclusion, induction of de novo synthesis of sphingolipids and inhibition of DEGS contribute to the anti-proliferative effects of celecoxib.

Benzoxazoles are DNA base bioisosteres and studies suggest that their derivatives have antiproliferative activities. Based on their antiproliferative activities they have been mostly studied as new generation anticancer drugs. In our study we exploited their antiproliferative effect, aiming to delineate bisbenzoxazole derivatives' (RHE 231 and RHE 238) potential antiinflammatory effect on mouse macrophages that are activated in vitro through danger signal LPS stimulation. RAW 267.4 mammalian macrophages were activated in the presence of our derivatives with or without danger mimic E. coli derived LPS. We present data that support the strong antiinflammatory activity of the bisbenzoxazole derivatives RHE 231 and RHE 238 on stimulated mammalian macrophages. There was a significant and substantial decrease in the production levels of TNF-$\alpha $, IL-1$\beta $, and IL-6 proinflammatory cytokines in the presence of RHE 231 and RHE 238. These molecules had an antiproliferative effect on the macrophages and, probably, this was their mechanism of action on the cells to alter their inflammatory functions. Our results show that bisbenzoxazole structures RHE 231 and RHE 238 have potential to be used as antiinflammatory drug agents.

3200 Objective: Iron plays a critical role in cell proliferation and survival making it a potential target for cancer therapy. Iron chelators have recently been shown to possess selective anti-neoplastic properties. Mimosine, a plant amino acid, acts as a potent iron chelator, but its use in gynecologic malignancies has yet to be tested. It is a naturally occurring plant amino acid known to arrest cell-cycle progression at the G1-S border in cultured cells. The objective of our study was to evaluate the anti-proliferative and pro-apoptotic effects of mimosine on human and rat ovarian cancer cells. Methods: Human (CaOV-3 & OvCAR) and rat (NuTu 19) ovarian cancer cell lines were treated for 24–72 hours with mimosine at varying doses ranging from 50 to 800 micro-molar concentrations. Untreated cells were used as a control. Cell viability was measured by MTS reduction assay and cell proliferation was determined by BrdU incorporation. Apoptosis was analyzed by DNA fragmentation. Iron challenge studies were performed to determine the role of iron in the cytotoxic effect of mimosine. Results: Mimosine demonstrated dose dependent anti-proliferative effects on all the ovarian cancer cells tested. Cell viability was inhibited over 70% at a dose of 200μM mimosine. Mimosine also inhibited DNA synthesis as revealed by BrdU incorporation assay. Fifty percent inhibition in DNA synthesis was observed at 100 μM dose level of mimosine. Addition of ferric ion effectively reversed the effects of mimosine, indicating that the effect of mimosine is mediated by iron chelation. In addition, mimosine induced apoptosis. DNA fragmentation analysis confirmed apoptosis. Further testing revealed mimosine to have significant dose-dependent antiproliferative effects on vulvar and cervical cancer cell lines and only a minimal effect on endometrial and colorectal cells. Conclusions: Mimosine, an iron chelator, has potent cytotoxic and anti-proliferative effects on a human and rat ovarian cancer cells. Iron challenge studies imply that the anti-proliferative effect of mimosine is mediated by iron chelation. Mimosine induced apoptosis. No significant financial relationships to disclose.

It is now well documented that certain anesthetic techniques may influence long term outcome in cancer patients undergoing surgery. More recently, local anesthetics proved certain antiproliferative effects in cancer cells. In our study, we aimed to investigate if lidocaine has antiproliferative effects in human hepatocarcinoma cells and to identify possible mechanisms of these effects. We investigated the inhibitory effect of different concentrations of lidocaine on the proliferation of cultured HepG2 human hepatocarcinoma cells and LX2 normal liver fibroblasts. Cells were exposed to nine different concentrations of lidocaine for 72h. MTT assay was used to investigate HepG2 and LX2 proliferation while Western blotting was used for detection of p53 expression level. Our data showed that lidocaine inhibited cell proliferation in a concentration-dependent manner in both HepG2 and LX2. The antiproliferative effects of lidocaine in LX2 were significantly diminished as compared with those in HepG2 (p< 0.001). Similarly, the expression level of p53 was significant decreased in HepG2 lines treated with lidocaine as compared with control and LX2 (p = 0.0241). In clinically relevant concentrations, lidocaine had significant antiproliferative effects on human hepatocarcinoma cells. These effects were time and dose-dependent. One of the possible mechanisms of these effects is by modifying the P53 expression level. The relevance of these findings in clinical practice is limited; clinical impact of these effects on the outcome of patients with hepatocarcinoma undergoing surgery or minimal invasive procedures needs to be demonstrated in future animal models and clinical studies.

MK615 is produced from Japanese apricot and contains several cyclic triterpenes, such as oleanolic and ursolic acids. MK615 was shown to strongly suppress cutaneous in-transit metastasis in a patient with malignant melanoma. The present investigation was undertaken to clarify the antitumor effects of MK615 in vitro and in vivo. Several human cancer cell lines were exposed to MK615 for 7 days to examine its antiproliferative effects. The effect of MK615 on in vivo growth of human pancreatic cancer MIAPaCa-2 cells was also examined. MK615 inhibited the growth of several human cancer cell lines in a concentration-dependent way. Pancreatic cancer MIAPaCa-2 cells were highly sensitive to the growth-inhibiting effects of MK615. Treatment with MK615 preferentially induced cell death in human cancer cells while sparing normal cells such as human umbilical vein endothelial cells (HUVEC) and mouse bone marrow cells. When MIAPaCa-2 cells were incubated with MK615 in the presence of antioxidant, growth-inhibition was significantly reduced, and MK615 induced the accumulation of reactive oxygen species in cancer cells but not in HUVEC. MK615, in both the presence and absence of gemcitabine, significantly inhibited the growth of human pancreatic cancer cells as xenografts without apparent adverse effects. MK615, a supplement produced from Japanese apricot, may have therapeutic value in treating human cancers through a reactive oxygen species-dependent mechanism.

MK615 is produced from Japanese apricot and contains several cyclic triterpenes, such as oleanolic and ursolic acids. MK615 was shown to strongly suppress cutaneous in-transit metastasis in a patient with malignant melanoma. The present investigation was undertaken to clarify the antitumor effects of MK615 in vitro and in vivo. Several human cancer cell lines were exposed to MK615 for 7 days to examine its antiproliferative effects. The effect of MK615 on in vivo growth of human pancreatic cancer MIAPaCa-2 cells was also examined. MK615 inhibited the growth of several human cancer cell lines in a concentration-dependent way. Pancreatic cancer MIAPaCa-2 cells were highly sensitive to the growth-inhibiting effects of MK615. Treatment with MK615 preferentially induced cell death in human cancer cells while sparing normal cells such as human umbilical vein endothelial cells (HUVEC) and mouse bone marrow cells. When MIAPaCa-2 cells were incubated with MK615 in the presence of antioxidant, growth-inhibition was significantly reduced, and MK615 induced the accumulation of reactive oxygen species in cancer cells but not in HUVEC. MK615, in both the presence and absence of gemcitabine, significantly inhibited the growth of human pancreatic cancer cells as xenografts without apparent adverse effects. MK615, a supplement produced from Japanese apricot, may have therapeutic value in treating human cancers through a reactive oxygen species-dependent mechanism.

Oleuropein (OL) and hydroxytyrosol (HT), the main olive oil polyphenols, possess anti-proliferative effects in vitro. Fatty acid synthase, a key anabolic enzyme of biosynthesis of fatty acids, plays an important role in colon carcinoma development. Our aim was to investigate whether gene expression of FAS, as well as its enzymatic activity, is regulated by HT and OL in two human colon cancer cell lines, as HT-29 and SW620. In addition, we investigated the effects of these polyphenols on growth and apoptosis in these cells. FAS gene expression and activity in treated HT-29 and SW620 cells were evaluated by real-time PCR and radiochemical assay, respectively. Cell growth and apoptosis, after polyphenols treatment, were measured by MTT test and flow cytometry, respectively. The inhibition of proliferation, detected after HT treatment, was mediated by an inhibition of FAS expression and its enzymatic activity in SW620 cells, while the anti-proliferative effect in HT-29 cells seems to be independent from FAS. OL exerted an anti-proliferative effect only on SW620 cells with a mechanism which excluded FAS. Olive oil polyphenols used were able to induce apoptosis in both cell lines studied. The increase of apoptosis in these cells was accompanied by the block of cell cycle in the S phase. This study demonstrates that HT and OL may induce anti-proliferative and pro-apoptotic effects only in certain human colorectal cancer cell types. These effects are FAS mediated only in SW620 cells after treatment with HT.

BackgroundLactobacillus plantarum, a major species of Lactic Acid Bacteria (LAB), are capable of producing postbiotic metabolites (PM) with prominent probiotic effects that have been documented extensively for rats, poultry and pigs. Despite the emerging evidence of anticancer properties of LAB, very limited information is available on cytotoxic and antiproliferative activity of PM produced by L. plantarum. Therefore, the cytotoxicity of PM produced by six strains of L. plantarum on various cancer and normal cells are yet to be evaluated.MethodsPostbiotic metabolites (PM) produced by six strains of L. plantarum were determined for their antiproliferative and cytotoxic effects on normal human primary cells, breast, colorectal, cervical, liver and leukemia cancer cell lines via MTT assay, trypan blue exclusion method and BrdU assay. The toxicity of PM was determined for human and various animal red blood cells via haemolytic assay. The cytotoxicity mode was subsequently determined for selected UL4 PM on MCF-7 cells due to its pronounced cytotoxic effect by fluorescent microscopic observation using AO/PI dye reagents and flow cytometric analyses.ResultsUL4 PM exhibited the lowest IC50 value on MCF-7, RG14 PM on HT29 and RG11 and RI11 PM on HL60 cell lines, respectively from MTT assay. Moreover, all tested PM did not cause haemolysis of human, dog, rabbit and chicken red blood cells and demonstrated no cytotoxicity on normal breast MCF-10A cells and primary cultured cells including human peripheral blood mononuclear cells, mice splenocytes and thymocytes. Antiproliferation of MCF-7 and HT-29 cells was potently induced by UL4 and RG 14 PM respectively after 72 h of incubation at the concentration of 30% (v/v). Fluorescent microscopic observation and flow cytometric analyses showed that the pronounced cytotoxic effect of UL4 PM on MCF-7 cells was mediated through apoptosis.ConclusionIn conclusion, PM produced by the six strains of L. plantarum exhibited selective cytotoxic via antiproliferative effect and induction of apoptosis against malignant cancer cells in a strain-specific and cancer cell type-specific manner whilst sparing the normal cells. This reveals the vast potentials of PM from L. plantarum as functional supplement and as an adjunctive treatment for cancer.

Adzuki beans have been historically utilized for both culinary and medicinal purposes in Japan. Lectin derived from Japanese red adzuki beans (JABs, Vigna angularis) exhibits several biological effects; however, to our knowledge, no detailed reports have been published on this topic. We purified lectin from adzuki beans to evaluate its impact on the proliferative activity of cancer cells and establish its biological profile. The Japanese red adzuki bean lectin (JABL) was purified using thyroglobulin-Sepharose 4B and evaluated for blood and sugar specificity and its effect on B16, LM8, Ehrlich ascites, HepG2, HeLa, and Colo679 cell proliferation compared with those of concanavalin A (ConA, Canavalia ensiformis) lectin. The molecular weight of JABL was 60kDa. JABL showed specificity to thyroglobulin, fetuin, and rabbit erythrocytes, but not to sheep and horse erythrocytes. Additionally, JABL showed no resistance to chymotrypsin but exhibited weak resistance at temperatures>60°C. JABL exerted significantly stronger antiproliferative effects than that of the control on human and mouse cancer cells in a concentration-dependent manner. JABL demonstrated 30%-40% superior antiproliferative activity against Colo679 and B16 cells compared to that against other cells. JABL activity was weaker than ConA activity (approximately 80%-90%) but equivalent to red kidney bean (Phaseolus vulgaris) lectin activity. No inhibitory effect of JABL on TNF-α was observed, which is typically observed with bean lectins. Our results show that JABL might exert antiproliferative effects on mouse and human cancer cells, making it a potential chemopreventive agent for cancer. PRACTICAL APPLICATION: Japanese red adzuki beans are popular in Asia, especially Japan. In Japan, the adzuki bean is a staple food and used in Japanese confectionery for celebrations. Adzuki bean lectin was purified using thyroglobulin-Sepharose 4B. The purified lectin showed specificity for rabbit erythrocytes and anticancer activity in mouse and human cells. The lectin retained its biological activity even when subjected to temperatures exceeding 60°C. Thus, adzuki bean lectin has the potential to be used as a bioactive and anticancer agent in medical research.

Purpose: It has been demonstrated ellagic acid can inhibit tumor growth. However, the mechanism that elicits the antiproliferative effect of ellagic acid is poorly understood. Our objective in this study was to evaluate the biological activity of ellagic acid by comparing the anti-proliferative effect and the apoptotic pathway of ellagic acid between the 2 human breast cancer cell lines. Methods: The MCF-7 and MDAMB-231 human breast cancer cell lines were used as cell models. The anti-proliferstive effect was evaluated by using a MTT assay. The cell cycle was analyzed by flow cytometry. Western blotting was performed to show the expressions of bcl-xL, cytochrome c, surviving, c-fos and pS2. Results: The ellagic acid in the MDA-MB-231 cells showed significant antiproliferative effects with dose dependent pattern. The antiproliferative effects in MCF-7 cells were observed in only at a high concentration. Ellagic acid had no effect on the cell cycle in both breast cancer cells. In MDA-MB-231, the expression of bcl-xL was decreased with the decreasing concentration of ellagic acid. The expression of cytochrome c in the cytosol was increased with the decreased expression of bcl-xL. Ellagic acid also decreased the expression of survivin. In the MCF-7 cells, the expressions of bcl-xL and cytochrome c showed no change after treatment with ellagic acid even at a high dose. Ellagic acid was able to induce an upregulation of c-fos and pS2 protein in MCF-7. Conclusion: Ellagic acid has an anti-proliferative effect in the MDA-MB231 cells. This effect of ellagic acid is through the intrinsic pathway in MDA-MB-231 cells. However, the expression of bcl-xL showed no change in the MCF-7 cells. Ellagic acid has a different anti-proliferative effect between the two human breast cancer cell lines.

Ethanol extract of garlic peels (GPE) was investigated for its antiproliferative effects on human cancer cell lines. Human lung cancer cell line A549 treated with 500 μg/mL GPE resulted in the growth inhibition of A549 by 90%. In stomach cancer cell AGS proliferation inhibition activity, GPE showed 45% and 71% inhibition of AGS growth at 1,000 μg/mL and 2,000 μg/mL, respectively. GPE inhibited the growth of the breast cancer cells MCF-7 effectively at low concentration and showed 78% and 90% inhibitions of MCF-7 growth at 200 μg/mL and 500 μg/mL , respectively. GPE showed very significant antiproliferation effect on liver cancer cell line Hep3B and inhibited Hep3B cell growth by 57% at 100 μg/mL, and the inhibition’s rate increased up to 87% at 500 μg/mL. Antiproliferation effect of GPE on colorectal cancer cell HT-29 showed 15% reduction of HT-29 cell growth at 200 μg/mL and the growth rate was reduced in a dose dependent manner up to 1,000 μg/mL. These results indicated that GPE had high antiproliferation effects on breast and liver cancer cell lines at low concentrations (200 μg/mL), and by higher concentrations over 500 μg/mL, GPE inhibited the growth of A549 and HT-29. The results of our study suggested the potential use of garlic peels for use as an excellent antiproliferative substance for human cancer cells.

Histone deacetylases (HDACs) play a major role in the regulation of chromatin structure and gene expression by changing acetylation status of histone and non-histone proteins. MS-275 (entinostat, MS) is a well-known benzamide-based HDACI and Salermide (SAL), a reverse amide compound HDACI, have antiproliferative effects on several human cancer cells. In this study, we aimed to investigate the effects of HDACIs (MS and SAL) alone and/or combined use with EF24 (EF), a novel synthetic curcumin analog, on human pancreatic cancer cell line (BxPC-3). In vitro, BxPC-3 cells were exposed to varying concentrations of MS, SAL with or without EF, and their effects on cell viability, acetylated Histone H3 and H4 levels, cytotoxicity, and cleaved caspase 3 levels, and cell cycle distribution were measured. The viability of BxPC-3 cells decreased significantly after treatment with EF, MS and SAL treatments. MS and SAL treatment increased the acetylation of histone H3 and H4 in a dose dependent manner. MS and SAL alone or combined with EF were increased the number of cells in G1 phase. In addition, treatment with agents significantly decreased the ratio of cell in G2/M phase. There were significant dose-dependent increases at cleaved Caspase 3 levels after MS treatment but not after SAL treatment. Our results showed that HDAC inhibitors (MS and SAL), when combined with EF, may effectively reduce pancreatic cancer cell (BxPC-3) progression and stop the cell cycle at G1 phase. Further molecular analyses are needed to understand the fundamental molecular consequences of HDAC inhibition in pancreas cancer cells.

The HH signaling pathway is critical for normal embryonic development, tissue patterning and cell differentiation. Aberrant HH signaling is involved in multiple human cancers. HH signaling involves a multi-protein cascade activating the GLI proteins that transcriptionally regulate HH target genes. We have recently reported that HH signaling is essential for human colon cancer cell survival, and that inhibition of this signal induces DNA damage and extensive cell death. The current study demonstrates that HH signaling regulates human telomerase reverse transcriptase (hTERT), which determines the limitless replication potential of cancer cells. Suppression of both GLI1 and GLI2 functions by exogenous expression of a C-terminus truncated GLI3 repressor mutant (GLI3R), or by GANT61, a pharmacologic inhibitor of GLI1 and GLI2 transcriptional activity, reduced hTERT protein expression in human colon, prostate and brain cancer (glioblastoma, GBM) cell lines. Exogenous expression of a constitutively active mutant of GLI2, GLI2m, significantly increased hTERT transcription, protein expression, and hTERT promoter-luciferase activity, in human colon cancer cells. Exposure to GANT61 inhibited hTERT mRNA expression in human colon cancer cells. Insilico analysis of the hTERT promoter revealed 7 putative GLI binding sites suggesting a direct transcriptional mode of regulation of hTERT by GLI. Chromatin immunoprecipitation (ChIP) analysis with GLI1 or GLI2 antibodies precipitated fragments of the hTERT promoter in human colon cancer cells, indicating a direct interaction between GLI proteins and the hTERT promoter. The binding between GLI2 and the promoter of hTERT was significantly reduced upon exposure to GANT61. Of interest, exogenous expression of GLI1 or GLI2m in non-cancerous 293T cells failed to alter the levels of hTERT mRNA and protein, or hTERT promoter-luciferase activity. Further, ChIP analysis of GFP-tagged GLI2 did not precipitate the hTERT promoter in 293T cells, in contrast to events in malignant cells. GLI2m also increased telomerase activity in human colon cancer cells, while GANT61 reduced the telomerase activity in human colon, prostate and GBM cells. These results demonstrate that the HH signaling pathway directly regulates hTERT by direct interaction with GLI in cancer cells in contrast to non-transformed cells, and identify a previously unknown role of the HH/GLI axis in regulating the replication potential of cancer cells. These findings are of significance in understanding important regulatory mechanisms that determine the role of HH/GLI signaling in cancer cell survival. Citation Format: Tapati Mazumdar, Ranjodh Sandhu, Maha Qadan, Victoria Magloire, Akwasi Agyeman, Bibo Li, Janet A. Houghton. Hedgehog signaling at the level of GLI transcriptionally regulates hTERT in human cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1790A. doi:10.1158/1538-7445.AM2013-1790A

This research examined the effects of Compositae extract on the inhibition of proliferation and apoptosis in human breast and human gastric cancer cells. Compositae extracts which is used in the experiment are Taraxacum coreanum (TC), Youngia sonchifolia (YS) and Ixeris dentata (ID). The proliferation of SK-BR-3, MDA- MB-231 and AGS cells were investigated by MTT assay. ID and YS extracts inhibited proliferation of SK-BR-3, MDA-MB-231 and AGS cells in a dose-dependent manner, but TC have barely affected. In addition, the most effec- tive extract was ID. To assess the apoptosis of ID extract, the nuclei of human cancer cells were stained with DAPI solution respectively. Chromatin condensation, indicated apoptosis, was increased in a dose-dependent manner. We investigated change of ID extract-induced apoptosis proteins on human cancer cells by western blot analysis. The level of Bcl-2 decreased, whereas the level of Bax, cleaved-PARP increased in dose-dependent manner compared with non-treatment. Also Bax/Bcl-2 ratio, which is used in clinical indicator of apoptosis, was increased at ID extract treat- ment group compared with non-treatment. Moreover the Bax/Bcl-2 ratio of MDA-MB-231 cell was significantly increased as against SK-BR-3, AGS cells. These results indicated that ID extract have anti-proliferation effect better than YS or TC, and induced apoptosis in human breast cancer MDA-MB-231 cell better than human breast cancer SK- BR-3 cell, human gastric cancer. Even if further research is needed, ID can be developed as a chemopreventive or therapeutic agent of breast cancer.