Tumor Inhibitory Activity Research Articles

Regio-selective PEGylation of 14-deoxy-11,12-didehydroandrographolide and their biological evaluation

Poor water solubility limits the clinical use of 14-deoxy-11,12-didehydroandrographolide (DA). To develop a simple and efficient approach to improving water solubility of DA, polyethylene glycol methyl ether (mPEG350, average MW=350) as hydrophilic group is employed. Two PEGylated DA derivatives DA-1 (mPEG350 at C19-position) and DA-2 (mPEG350 at C3-position) are synthesized and evaluated to inhibit the cell proliferation of HepG-2 cells in vitro. As expected, the aqueous solubility of DA-1 and DA-2 is significantly improved (ca. 200 mg/mL, 25 °C), and both exhibit good partition coefficient (log P≥1.6). It is found that DA-1 shows tumor-inhibition activity and more than 60% cell inhibition is obtained.

Lung cancer inhibitory activity of dietary berries and berry polyphenolics

BACKGROUND: Blueberry (BB) and black raspberry (BRB) have been shown to be chemopreventive against estrogenmediated breast cancer in pre-clinical studies. However, therapeutic efficacy of these berries against lung cancer is not known. METHODS: In this study we investigated i) relative efficacy of individual anthocyanidins vs. respective anthocyanins, ii) relative antiproliferative activity of mixture of anthocyanidins compared to individual anthocyanidins, iii) antitumor activity of dietary BB, iv) Tumor inhibitory activity of diet supplemented with BB, alone and in combination with BRB, against lung tumor xenograft using nude mice, and finally, v) the efficacy of select polyphenolics present in BB and BRB against lung tumor xenograft. RESULTS: Our findings indicated that individual anthocyanidins (aglycones) were significantly more potent (2-3 fold lower IC50) in inhibiting the non-small-cell lung cancer (NSCLC) cell growth vs. respective anthocyanins (glycones). Further, anthocyanidins mixture at equimolar concentrations exhibited synergistic antiproliferative activity vs. individual anthocyanidins. When tested against NSCLC (A549 and H1299) cells in nude mice, dietary BB (7.5%, w/w) showed >40% reduction in tumor volume against H1299 xenografts. The maximal growth inhibition occurred with 5% BB dose, with no additional protection occurring at a higher dose (7.5%). However, somewhat lower protection was found when the BB diet initiated prior to tumor cell inoculation. The mixture of BB (5%, w/w) and BRB (2.5%) resulted in higher inhibition of tumor growth vs. BB alone (71% vs 42%). Likewise, a combination of delphinidin (bioactive of BB) and punicalagins (a bioactive of BRB, which gets converted to ellagic acid in vivo) showed higher tumor growth inhibition compared to delphinidin. CONCLUSIONS: The therapeutic effects of the berries and berry polyphenolics observed against lung cancer in this study are highly encouraging. Further investigation into the mechanism of action of the combinations of the berry bioactives will be valuable for clinical use of this potent natural product against lung cancer.

Overcoming Therapeutic Resistance by Targeting Cancer Inflammation.

Tumor-infiltrating myeloid cells are a prominent feature of most solid malignancies. This inflammatory immune response, driven by tumor-intrinsic signaling pathways, is a major checkpoint to therapeutic efficacy achieved with immunotherapy and standard cytotoxic therapies. To overcome therapeutic resistance mediated by cancer inflammation, ongoing clinical trials are evaluating strategies that (1) deplete myeloid cells from tumors, (2) inhibit tumor-promoting properties of myeloid cells, and (3) redirect myeloid cells with tumor-inhibitory activity.

Epigenetics Reactivation of Nrf2 in Prostate TRAMP C1 Cells by Curcumin Analogue FN1.

It has previously been shown that curcumin can effectively inhibit prostate cancer proliferation and progression in TRAMP mice, potentially acting through the hypomethylation of the Nrf2 gene promoter and hence activation of the Nrf2 pathway to enhance cell antioxidative defense. FN1 is a synthetic curcumin analogue that shows stronger anticancer activity than curcumin in other reports. We aimed to explore the epigenetic modification of FN1 that restores Nrf2 expression in TRAMP-C1 cells. Stably transfected HepG2-C8 cells were used to investigate the effect of FN1 on the Nrf2- antioxidant response element (ARE) pathway. Real-time quantitative PCR and Western blotting were applied to study the influence of FN1 on endogenous Nrf2 and its downstream genes. Bisulfite genomic sequencing (BGS) and methylated DNA immunoprecipitation (MeDIP) were then performed to examine the methylation profile of the Nrf2 promoter. An anchorage-independent colony-formation analysis was conducted to examine the tumor inhibition activity of FN1. Epigenetic modification enzymes, including DNMTs and HDACs, were investigated by Western blotting. The luciferase reporter assay indicated that FN1 was more potent than curcumin in activating the Nrf2-ARE pathway. FN1 increased the expression of Nrf2 and its downstream detoxifying enzymes. FN1 significantly inhibited the colony formation of TRAMP-C1 cells. BGS and MeDIP assays revealed that FN1 treatment (250 nM for 3 days) reduced the percentage of CpG methylation of the Nrf2 promoter. FN1 also downregulated epigenetic modification enzymes. In conclusion, our results suggest that FN1 is a novel anticancer agent for prostate cancer. In the TRAMP-C1 cell line, FN1 can increase the level of Nrf2 and downstream genes via activating the Nrf2-ARE pathway and inhibit the colony formation potentially through the decreased expression of keap1 coupled with CpG demethylation of the Nrf2 promoter. This CpG demethylation effect may come from decreased epigenetic modification enzymes, such as DNMT1, DNMT3a, DNMT3b, and HDAC4.

Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

DAB2IP in cancer.

DOC-2/DAB2 is a member of the disable gene family that features tumor-inhibiting activity. The DOC-2/DAB2 interactive protein, DAB2IP, is a new member of the Ras GTPase-activating protein family. It interacts directly with DAB2 and has distinct cellular functions such as modulating different signal cascades associated with cell proliferation, survival, apoptosis and metastasis. Recently, DAB2IP has been found significantly down regulated in multiple types of cancer. The aberrant alteration of DAB2IP in cancer is caused by a variety of mechanisms, including the aberrant promoter methylation, histone deacetylation, and others. Reduced expression of DAB2IP in neoplasm may indicate a poor prognosis of many malignant cancers. Moreover, DAB2IP stands for a promising direction for developing targeted therapies due to its capacity to inhibit tumor cell growth in vitro and in vivo. Here, we summarize the present understanding of the tumor suppressive role of DAB2IP in cancer progression; the mechanisms underlying the dysregulation of DAB2IP; the gene functional mechanism and the prospects of DAB2IP in the future cancer research.

Suppression of Her2/Neu mammary tumor development in mda-7/IL-24 transgenic mice.

Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) encodes a tumor suppressor gene implicated in the growth of various tumor types including breast cancer. We previously demonstrated that recombinant adenovirus-mediated mda-7/IL-24 expression in the mammary glands of carcinogen-treated (methylnitrosourea, MNU) rats suppressed mammary tumor development. Since most MNU-induced tumors in rats contain activating mutations in Ha-ras, which arenot frequently detected in humans, we presently examined the effect of MDA-7/IL-24 on Her2/Neu-induced mammary tumors, in which the RAS pathway is induced. We generated tet-inducible MDA-7/IL-24 transgenic mice and crossed them with Her2/Neu transgenic mice. Triple compound transgenic mice treated with doxycycline exhibited a strong inhibition of tumor development, demonstrating tumor suppressor activity by MDA-7/IL-24 in immune-competent mice. MDA-7/IL-24 induction also inhibited growth of tumors generated following injection of Her2/Neu tumor cells isolated from triple compound transgenic mice that had not been treated with doxycycline, into the mammary fat pads of isogenic FVB mice. Despite initial growth suppression, tumors in triple compound transgenic mice lost mda-7/IL-24 expression and grew, albeit after longer latency, indicating that continuous presence of this cytokine within tumor microenvironment is crucial to sustain tumor inhibitory activity. Mechanistically, MDA-7/IL-24 exerted its tumor suppression effect on HER2+ breast cancer cells, at least in part, through PERP, a member of PMP-22 family with growth arrest and apoptosis-inducing capacity. Overall, our results establish mda-7/IL-24 as a suppressor of mammary tumor development and provide a rationale for using this cytokine in the prevention/treatment of human breast cancer.

Targeted Shiga toxin–drug conjugates prepared via Cu-free click chemistry

The main drawback of the anticancer chemotherapy consists in the lack of drug selectivity causing severe side effects. The targeted drug delivery appears to be a very promising strategy for controlling the biodistribution of the cytotoxic agent only on malignant tissues by linking it to tumor-targeting moiety. Here we exploit the natural characteristics of Shiga toxin B sub-unit (STxB) as targeting carrier on Gb3-positive cancer cells. Two cytotoxic conjugates STxB–doxorubicin (STxB–Doxo) and STxB–monomethyl auristatin F (STxB–MMAF) were synthesised using copper-free ‘click’ chemistry. Both conjugates were obtained in very high yield and demonstrated strong tumor inhibition activity in a nanomolar range on Gb3-positive cells.

New cycloartane triterpenes from the aerial parts of Cimicifuga heracleifolia

Twelve new cycloartane triterpenes (1–12), as well as five known constituents (13–17), were isolated from the aerial parts of Cimicifuga heracleifolia. Their structures were elucidated on the basis of extensive spectroscopic methods. Selected compounds were evaluated for their in vitro cytotoxicity against human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW-480) and inhibitory activity with STAT 3 signaling pathway.

Silencing JARID1B suppresses oncogenicity, stemness and increases radiation sensitivity in human oral carcinoma

PurposeOral squamous cell carcinoma (OSCC) is a major cause of human mortality globally and radiotherapy is one of the main treatment modalities, however its therapeutic effect is often limited by radioresistance. JARID1B is an epigenetic factor with reported oncogenic potential in various cancer types. We investigated the effect of JARID1B inhibition on migration and invasion of human OSCC cell lines, as well as on clinical patients' outcome. Materials and MethodsWound healing, matrigel invasion, Sulforhodamine B, and spheroid formation assays were used to characterize the signaling pathways of shJARID1B in response to radiation treatment. We evaluated the prognostic relevance of Jarid1b expression in a cohort of 81 OSCC patients. ResultsHuman OSCC cell lines, including SAS, HSC3, Cal27, TW2.6 and SCC4 cells, were used. shJARID1B cells significantly inhibited migration and invasion ability compared to their vector or wild type counterparts. Silencing shJARID1B significantly inhibited oral cancer stem cell activity and potentiated the tumor-inhibitory activity of radiation therapy in OSCC. Radiotherapy coupled with shJARID1B knockdown reduced mRNA levels of NQO1, KEAP1, NRF2, FOXO1, FOXO3, KLF4, OCT4, CD133, and Nanog in malignant OSCC cells. OSCC spheroid formation ability was markedly reduced in the shJARID1B cells. JARID1B overexpression is a dependent prognostic factor in OSCC patients. ConclusionsSilencing shJARID1B inhibits migration and invasion of human OSCC, reduces cancer stem cell activities and potentiates tumor-inhibiting radiotherapeutic effects. JARID1B knockdown prior to radiotherapy is a potential effective therapeutic strategy for the treatment of OSCC.

Role of p14ARF-HDM2-p53 axis in SOX6-mediated tumor suppression.

Sex-determining region Y box 6 (SOX6) has been described as a tumor-suppressor gene in several cancers. Our previous work has suggested that SOX6 upregulated p21Waf1/Cip1(p21) expression in a p53-dependent manner; however, the underlying mechanism has remained elusive. In this study, we confirmed that SOX6 can suppress cell proliferation in vitro and in vivo by stabilizing p53 protein and subsequently upregulating p21. Co-immunoprecipitation and immunocytofluorescence assays demonstrated that SOX6 can promote formation of the p14ARF-HDM2-p53 ternary complex by promoting translocation of p14ARF (p14 alternate reading frame tumor suppressor) to the nucleoplasm, thereby inhibiting HDM2-mediated p53 nuclear export and degradation. Chromatin immunoprecipitation combined with PCR assay proved that SOX6 can bind to a potential binding site in the regulatory region of the c-Myc gene. Furthermore, we confirmed that SOX6 can downregulate the expression of c-Myc, as well as its direct target gene nucleophosmin 1 (NPM1), and that the SOX6-induced downregulation of NPM1 is linked to translocation of p14ARF to the nucleoplasm. Finally, we showed that the highly conserved high-mobility group (HMG) domain of SOX6 is required for SOX6-mediated p53 stabilization and tumor inhibitory activity. Collectively, these results reveal a new mechanism of SOX6-mediated tumor suppression involving p21 upregulation via the p14ARF-HDM2-p53 axis in an HMG domain-dependent manner.

6-Bromo-2,3-Dioxoindolin Phenylacetamide Derivatives: Synthesis, Potent CDC25B, PTP1B Inhibitors and Anticancer Activity

A series of 6-bromo-2,3-dioxoindolin phenylacetamide derivatives was synthesized and evaluated for inhibitory activity against CDC25B and PTP1B. Most of the synthesized compounds showed potential inhibitory activities for CDC25B and PTP1B with compound 12 being the most potent (IC50=3.87 µmol/L and 2.98 µmol/L, respectively). Compound 12 also exhibited higher cytotoxic activity against three cancer cell lines (HeLa, A549 and HCT116). In addition, compound 12 delayed the potent tumor inhibitory activity in a colo205 xenograft model in vivo. Keywords: 2, 3-Dioxoindolin phenylacetamide, CDC25B, PTP1B, MTT, Phosphatase inhibitors, Anticancer activity.

Enhancing the anticancer effects of 5-fluorouracil: current challenges and future perspectives.

5-Flurouracil (5-FU), a pyrimidine analog, was originally designed to prevent tumor cell growth. However, since the identification of its tumor inhibitory activity in 1957, substantial evidence has demonstrated that 5-FU could also harness the host immune system to prevent cancer progression. 5-FU sensitizes tumor cells to Natural Killer (NK) and CD8 T cell-driven cytotoxicity. We have also recently shown that 5-FU could selectively eliminate Myeloid Derived Suppressor Cells (MDSCs), which accumulate during cancer progression and compromise anticancer immune responses. The ability of 5-FU to trigger direct tumor cell death, enhance immune effector cell activation and eliminate immunosuppressive MDSCs explains its capacity to relieve tumor-induced immunosuppression and restore anticancer immune responses. Combination therapies using 5-FU with other chemotherapeutic agents, immunomodulators, or vaccines have further enhanced the clinical benefit of 5-FU. Here, we discuss how the increased understanding of the immune-driven effects of 5-FU prompts the design of relevant cancer chemoimmunotherapy strategies.

The Antitumor Activity of Meconopsis Horridula Hook, a Traditional Tibetan Medical Plant, in Murine Leukemia L1210 Cells

Background: Meconopsis horridula Hook (M. horridula) has been used as a traditional Tibetan medicine to relieve heat and pain as well as mobilize static blood, and it is recognized as a good treatment for bruises. This study is the first trial to evaluate the tumor inhibitory activity of M. horridula extract and its underlying mechanism in the hope of providing evidence to support the anticancer function of M. horridula. Methods and Results: M. horridula extract was cytotoxic to L1210 cells in a dose- and time-dependent manner. SEM (scanning electron microscope) observation revealed obvious morphological changes in L1210 cells after M. horridula treatment. Flow cytometry analysis demonstrated that the extract dose-dependently induced early apoptosis. Additional apoptosis parameters, such as alterations in nuclear morphology and DNA damage, were also observed. Furthermore, M. horridula treatment induced G2/M arrest. M. horridula treatment significantly increased reactive oxygen species (ROS) production, suggesting that ROS are a key factor in M. horridula-induced apoptosis. Volatile constituent detection found 15 abundant chemicals in M. horridula, which may contribute to its anticancer effect. Conclusion: In conclusion, M. horridula extract induced L1210 cell apoptosis and inhibited proliferation through G2/M phase arrest, and ROS were involved in the process.

Induction of tumor inhibitory anti-angiogenic response through immunization with interferon Gamma primed placental endothelial cells: ValloVax™

BackgroundWhile the concept of angiogenesis blockade as a therapeutic intervention for cancer has been repeatedly demonstrated, the full promise of this approach has yet to be realized. Specifically, drugs such as VEGF-blocking antibodies or kinase inhibitors suffer from the drawbacks of resistance development, as well as off-target toxicities. Previous studies have demonstrated feasibility of specifically inducing immunity towards tumor endothelium without consequences of systemic autoimmunity in both animal models and clinical settings.MethodPlacenta-derived endothelial cells were isolated and pretreated with interferon gamma to enhance immunogenicity. Syngeneic mice received subcutaneous administration of B16 melanoma, 4 T1 mammary carcinoma, and Lewis Lung Carcinoma (LLC), followed by administration of control saline, control placental endothelial cells, and interferon gamma primed endothelial cells (ValloVax™). Tumor volume was quantified. An LLC metastasis model was also established and treated under similar conditions. Furthermore, a safety analysis in non-tumor bearing mice bracketing the proposed clinical dose was conducted.ResultsValloVax™ immunization led to significant reduction of tumor growth and metastasis as compared to administration of non-treated placental endothelial cells. Mitotic inactivation by formalin fixation or irradiation preserved tumor inhibitory activity. Twenty-eight day evaluation of healthy male and female mice immunized with ValloVax™ resulted in no abnormalities or organ toxicities.ConclusionGiven the established rationale behind the potential therapeutic benefit of inhibiting tumor angiogenesis as a treatment for cancer, immunization against a variety of endothelial cell antigens may produce the best clinical response, enhancing efficacy and reducing the likelihood of the development of treatment resistance. These data support the clinical evaluation of irradiated ValloVax™ as an anti-angiogenic cancer vaccine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0441-0) contains supplementary material, which is available to authorized users.

Mechanism of the Anticancer Effect of Lycopene (Tetraterpenoids).

Increasing evidence suggests that lycopene, a major carotenoid detected in human plasma, may be preventive against the formation and the development of different types of human cancers including prostate, breast, and lung cancer. Experimental studies demonstrated that lycopene inhibits the growth of various cancer cells of different organs and prevent chemically induced carcinogenesis in animal models. Although the excellent antioxidant property of lycopene is most likely the basis for its preventive role toward cancer, the direct anticancer activities of lycopene through multiple mechanisms are disclosed, including regulation of growth factor signaling, cell cycle arrest and/or apoptosis induction, and changes in antioxidant and phase II detoxifying enzymes. The anti-inflammatory activity of lycopene is also considered as an important determinant that suppresses the promotion and progression of carcinogenesis. Moreover, lycopene inhibits cell invasion, angiogenesis, and metastasis. Importantly, those activities have been shown to be exhibited at the physiologically attainable concentration in humans. Although the preclinical data strongly suggest an antitumor activity of lycopene, a number of epidemiological and intervention studies indicate that there is still no clear clinical evidence that supports its use for the prevention of those cancers. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the cancer prevention. Nonetheless, because of its multiple tumor-inhibitory activities, lycopene still remains to be an attractive and promising carotenoid that will potentially contribute to the prevention and treatment of human cancers. This chapter reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

The interactions of anticancer agents with tea catechins: current evidence from preclinical studies.

Tea catechins exhibit a broad range of pharmacological activities that impart beneficial effects on human health. Epigallocatechin-3-gallate (EGCG), one of the major tea catechins, has been widely associated with cancer prevention and treatment. In addition, tea catechins in combination with anticancer drugs are being evaluated as a new cancer treatment strategy. However, the interactions of anticancer drugs with tea catechins are largely unknown. Accumulated data indicate significant interactions between anticancer drugs and tea catechins, such as synergistic tumor inhibition or antagonist activity. Therefore, it is critical to understand comprehensively the effects of tea catechins on anticancer drugs. Focusing on evidence from preclinical studies, this paper will review the interactions between anticancer drugs and tea catechins, including pharmacodynamics and pharmacokinetics effects. We hope that by detailing the interactions between anticancer drugs and tea catechins, more attention will be directed to this important therapeutic combination in the future.

Studies of Human Interleukin 24

In this report we present our progress in the functional and structural studies of human interleukin 24 (hIL-24). Interleukins and interferons (cytokines) together with their cognate receptors form a `front-end' of convoluted signaling networks, responsible for an immune-response to the presence of various pathogens. Cytokines are subjected to vigorous research related to their role in human physiology and disease and potential therapeutic uses. After many years of intense studies, information on some of cytokines is absent or limited, partly because new members are still being identified as well as due to difficulties of generating significant amounts of active preparations. A sub-family of `IL-10-related cytokines' also called the cytokine receptor type 2 family (CRF2) comprises nine members. One of CRF2 members is interleukin 24 (IL-24). The most interesting biological feature of human IL-24 (hIL-24) is its tumor inhibitory activity, observed in vitro for several cancer cell lines. IL-24 signals through the receptor complex comprising the high-affinity chain (IL-22R1 or IL-20R1) and the secondary, low-affinity chain (IL-20R2). Structure of IL-24 is currently unknown, although it is expected to be similar to those of other members of the CRF2 family. However, in silica analysis indicates several differences in the molecule of IL-24 when compared to its close homologues. One of more interesting is lack of two canonical disulfide bonds, found in all other interleukins from the CRF2 family, due to missing needed Cys residues. While an alternative, unique disulfide bond in IL-24 is possible, the appropriate experimental evidence is missing. Native IL-24 is N-glycosylated. Although this modification appears dispensable for biological activity of related cytokines, its role in IL-24 is not clear. We have expressed insoluble hIL-24 in bacteria and refolded it subsequently into a soluble, functional form. The mass spectrometry analysis confirmed presence of a single disulfide bond. Our non-glycosylated variant of hIL-24 activates the cognate receptor as efficiently as commercial preparations from eukaryotic sources. We observed, however, that stability of refolded hIL-24 is somewhat compromised. Subsequently, we plan investigating the structural properties of this cytokine.

DAO-9 (2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole) exhibits p53 induced apoptogenesis through caspase-3 mediated endonuclease activity in murine carcinoma

One of the main strategies to inhibit the tumor growth is to promote the biochemical events leading to DNA degradation, which would eventually culminate in apoptosis. We have earlier reported that the 2,5-di(4-aryloylaryloxymethyl)-1,3,4-oxadiazole(DAO-9) possessed anti-cancer activity. To address the exact molecular mechanism underlying anti-cancer property, present study focused on evaluating the anti-tumor effect of the DAO-9 on murine ascites carcinoma cells using various in vivo and in vitro assays. The in vivo assays implicated a strong regression in tumor growth of ascites carcinoma after treatment which is due to apoptogenic efficacy as assessed through structural morphology of EAC cells by Giemsa, Acridine orange, Annexin V staining and FACS analysis. Nucleosomal DNA fragmentation induced by DAO-9 is due to activation of caspase-3 mediated DNAse as verified by endonuclease assays and immunoblot analysis. The caspase-3 activation mechanism is by induction of intrinsic cascade signaling molecules, such as p53, Bax, Bad and cytochrome c (cyt c) expression as verified by western blot. The results concluded that the tumor inhibiting activity of DAO-9 is due to activation of the apoptotic signaling cascade, which could be translated into targeted anti-cancer drug in the near future.

Chalcones derivatives as potent Cell division cycle 25B phosphatase inhibitors

To discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells. Nineteen 2′-hydroxy-4′-isoprenyloxychalcone derivatives (a-s) were evaluated the inhibition CDC25B activity. The enzymatic activities of the CDC25B catalytic domain were determined by monitoring the dephosphorylation of OMFP. Cell growth inhibition was detected by MTT assay. The results showed that sixteen compounds significantly inhibited cycle 25B phosphatase in vitro. Among, three compounds k, r and s had the best inhibition activity and significantly inhibited CDC25B with inhibition rates against CDC25B of 99.95%, 99.75%, and 97.77%, respectively, which is similar to the reference drugs Na3VO4 (98%). Cytotoxic activity assays showed compounds k and r are the potent against HCT116, HeLa, and A549 cells, moreover, compound k delayed the potent tumor inhibitory activity in a colo205 xenograft model in vivo.