MDA-MB-468 Research Articles

Podophyllotoxin-polyacrylic acid conjugate micelles: improved anticancer efficacy against multidrug-resistant breast cancer

BackgroundPodophyllotoxin (PPT) is a naturally occurring compound obtained from the roots of Podophyllum species, indicated for a variety of malignant tumors such as breast, lung, and liver tumors. This toxic polyphenol (PPT) exhibited significant activity against P-glycoprotein (P-gp) mediated multidrug-resistant (MDR) cancer cells. However, extremely poor water solubility, a narrow therapeutic window, and high toxicity have greatly restricted the clinical uses of PPT. Therefore, the present research was aimed to synthesize the water-soluble ester prodrug of PPT with polyacrylic acid (PAA), a water-soluble polymer by Steglich esterification reaction, and to screen it for assay, solubility, in vitro hemolysis, in vitro release, and in vitro anticancer activity.ResultsThe Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy results revealed the successful synthesis of podophyllotoxin-polyacrylic acid conjugate (PPC). The assay and saturation solubility of the prodrug is found to be 64.01 ± 4.5% and 1.39 ± 0.05 mg/mL (PPT equivalent) respectively. The PPC showed CMC (critical micelle concentration) of 0.430 mg/mL in distilled water at room temperature. The PPC micelles showed a mean particle size of 215 ± 11 nm with polydispersity index (PDI) of 0.193 ± 0.006. Further, the transmission electron microscope (TEM) results confirmed the self-assembling character of PPC into micelles. The PPC caused significantly less hemolysis (18.6 ± 2.9%) than plain PPT solution. Also, it demonstrated significantly (p < 0.01) higher in vitro cytotoxicity against both sensitive as well as resistance human breast cancer cells (MCF-7 and MDA MB-231) after 48 h of treatment.ConclusionThe obtained study results clearly revealed the notable in vitro anticancer activity of PPT following its esterification with PAA. However, further in vivo studies are needed to ascertain its efficacy against a variety of cancers.

Synthesis, anticancer evaluation and molecular docking studies of 1,3,4-oxadiazole linked resveratrol derivatives

Abstract A new series of 1,3,4-Oxadiazole linked Resveratrol (9a-j) have been synthesized and characterized by 1HNMR, 13CNMR, ESI-MS spectral analysis. The in vitro cytotoxicity effects of synthesized compounds were evaluated against four different human cancer cells including MCF-7, MDA MB-231 (Breast) and A549 (Lung) cell lines. The biological results showed that most of the compounds significantly prevented the proliferation of tested cancer cells.In particular, compound 9b and 9j showed potent anticancer activities against MCF-7 (IC50 = 1.56, 0.45 µM, respectively), A549 (IC50 = 0.11, 1.11 µM, respectively) MDA-MB-231 (IC50 = 1.22, 1.98 µM, respectively). Molecular docking studies revealed that compound 9b selectively occupy the colchicine binding site of the tubulin polymer.

Lysophosphatidic acid-RAGE axis promotes lung and mammary oncogenesis via protein kinase B and regulating tumor microenvironment

BackgroundReceptor for advanced glycation end products (RAGE) is a multi-ligand transmembrane receptor of the immunoglobulin superfamily. Lysophosphatidic acid (LPA) is a ligand for RAGE and is involved in physiological and pathophysiological conditions including cancer. However, RAGE-LPA axis is unexplored in lung and mammary cancer.MethodsRAGE was silenced in A549, MDA MB-231 and MCF7 using RAGE shRNA. For in vitro tumorigenesis, we performed wound healing, colony formation, cell proliferation and invasion assays. Evaluation of expression of oncogenes, EMT markers and downstream signaling molecules was done by using western blot and immunohistochemistry. For subcellular expression of RAGE, immunofluorescence was done. In vivo tumorigenesis was assessed by intraperitoneal injection of cancer cells in nude mice.ResultsHere we show RAGE mediated profound increase in proliferation, migration and invasion of lung and mammary cancer cells via LPA in Protein kinase B (PKB) dependent manner. LPA mediated EMT transition is regulated by RAGE. In vivo xenograft results show significance of RAGE in LPA mediated lung and mammary tumor progression, angiogenesis and immune cell infiltration to tumor microenvironment.ConclusionOur results establish the significance and involvement of RAGE in LPA mediated lung and mammary tumor progression and EMT transition via RAGE. RAGE-LPA axis may be a therapeutic target in lung and mammary cancer treatment strategies.EdVB1f1yrz4Do4i3nWt_5KVideo

Assessment of replication of bovine herpesvirus type 4 in human glioblastoma and breast cancer cells as a potential oncolytic virus.

Oncolytic viruses have been extensively used in cancer treatment due to their tropism, selective replication only in tumor cells, and possible synergic interaction with other therapeutics. Different researchers have demonstrated that bovine herpesvirus 4 (BoHV-4), a member of the gammaherpesviridae family, has oncolytic potential in some human-origin cancer cell lines like glioma through the selective replication strategy. Using four apoptosis detection methods, namely MTT, LDH, TUNEL, and Annexin V assays, we evaluated the apoptotic effect of BoHV-4 Movar33/63 reference strain along with a recombinant BoHV-4 expressing EGFP in U87 MG cells (human glioblastoma cell line), MDA MB-231 (human breast cancer cell line), and MCF10a (non-tumorigenic human mammary epithelial cell line). Our findings indicate that this virus can replicate and induce apoptosis in these cell lines and hinder in vitro proliferation in a dose-dependent manner. In conclusion, BoHV-4 has in vitro potential as a novel oncolytic virus in human cancer therapy. However, its replication potential in the MCF10a cells as a non-tumorigenic human mammary epithelial cell line is a concern in using this virus in cancer therapy, at least against human mammary tumors. Further studies must therefore be conducted to examine the specific apoptotic pathways induced by this virus to move on to further experiments.

Radiation and Gold Nanoparticle Immunomodulation in MDA MB 231 Mouse Breast Cancer Model

Radiation and Gold Nanoparticle Immunomodulation in MDA MB 231 Mouse Breast Cancer Model

Capsaicin suppresses breast cancer cell viability by regulating the CDK8/PI3K/Akt/Wnt/β‑catenin signaling pathway

Breast cancer displays high morbidity and mortality. Despite exerting certain effects, traditional treatments cannot eliminate every cancer cell and may kill normal cells due to inaccurate targeting. However, as a traditional Chinese medicine, capsaicin, an active compound extracted from chili peppers, has displayed potent anticarcinogenic activities in vitro and in vivo, but the underlying mechanism is not completely understood. The pharmacological effects of capsaicin on tumors was evaluated in MDA MB 231 breast cancer cells. The MTT, cell scratch assay, cell cycle analysis, cell transfection, reverse transcription-quantitative PCR and western blotting were performed to investigate the potential antitumor mechanisms of capsaicin. In the present study, the potential anticancer mechanism underlying capsaicin in MDA-MB-231 cells in vitro was investigated. Capsaicin significantly inhibited MDA-MB-231 breast cancer cell viability and migration compared with the control group. The flow cytometry results indicated that capsaicin induced G2/M cell cycle arrest in MDA-MB-231 cells. In addition, capsaicin significantly reduced the expression of cyclin-dependent kinase 8 (CDK8) in breast cancer cells compared with the control group. Moreover, LV-CDK8 small interfering RNA-transduced MDA-MB-231 cells displayed lower CDK8 mRNA and protein expression levels compared with LV-negative control-shRNA-transduced cells. Furthermore, capsaicin significantly reduced the expression levels of phosphorylated (p)-PI3K, p-Akt, Wnt and β-catenin in vitro compared with the control group. Collectively, the results of the present study suggested that capsaicin inhibited breast cancer cell viability, induced G2/M cell cycle arrest, reduced CDK8 expression levels, decreased the phosphorylation of PI3K and Akt and downregulated Wnt and β-catenin expression levels in MDA-MB-231 cells.

Synergistic effect of curcumin, piperine and resveratrol in MCF-7 and MDA MB-231 breast cancer cells.

Breast cancer is the type of cancer that kills more women in the world and the conventional cancer treatment has high costs and many side effects. The bioactive compounds from diet alone or in combination with others substances may be a potential source for the prevention and treatment of breast cancer. The aim was to investigate the effect of curcumin, piperine and resveratrol alone and associated in MCF-7 and MDA-MB-231 breast cancer cells culture. Curcumin, piperine and resveratrol showed cytotoxicity for MCF-7 and MDA-MB-231 cells with IC50 values of 24.50 μM, 94.50 μM and 131.00 μM, and 23.30 μM, 276.00 μM and 306.00 μM, respectively. The combination of curcumin+piperine, curcumin+resveratrol, piperine+resveratrol showed synergy in MCF-7 cells, and piperine+resveratrol in MDA-MB-231 cells. We conclude that the combination of bioactive compounds presents in diet as curcumin, piperine and resveratrol is better than used in isolated forms, and these results may be useful in future clinical trials with breast cancer.

Artemesiaannua L. Silver Nanoparticles Exhibit Anticancer Activity by ROS mediated apoptosis in MDA-MB-231 Cells

Aim of this study was to investigate the growth inhibitory effect of Artemesisannua L. silver nanoparticles(A.annuaAgNPS) on human triple negative breast cancer tumor cell line MDA-MB-231. Cells werecultured and treated with A.annua water extract and A.annuaAgNPS to determine the half inhibitoryconcentration (IC50). Oxidative stress was determined using lipid peroxidation (LPO), ROS generation andby determining the levels of antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH).Further, the mechanism of apoptotic induction was assessed by DNA fragmentation analyses. We observedthat A.annuaAgNPS significantly caused growth inhibition by increasing levels of LPO and ROS, in a dosedependent manner with reduced level of endogenous antioxidant enzymes. Increased shear in genomic DNAfrom MDA MB231 cells treated with A.annuaAgNPS shows apoptosis to be the cause of cell cell death. Weconclude that A.annuaAgNPS can be useed as a therapeutic agent against breast cancer.

Design, Synthesis, and Anticancer Activity of Substituted Styryl Incorporated Quinazoline Derivatives

A novel series of substituted aryl ethynyl incorporated quinazolines has been synthesized, and their molecular structures have been characterized by1H and 13C NMR, and mass spectra. The products have been tested for their preliminary anticancer activity against human cancer cell lines like MCF-7 (human breast cancer), A549 (human lung cancer), DU-145 (human prostate cancer), and MDA MB-231 (human breast cancer). Some compounds are characterized by potent activity.

Design, Synthesis, and Anticancer Activity of Bis-isoxazole Incorporated Benzothiazole Derivatives

A novel series of bis-isoxazole incorporated benzothiazole derivatives has been designed and synthesized. Molecular structures of the compounds have been confirmed by 1H and 13C NMR, and mass spectra. All products have been tested for their in vitro anticancer activity against breast MCF-7 and MDA MB-231, lungs A549, and prostate DU-145 cancer cell lines using the MTT assay and etoposide as a standard drug. Most of the compounds have demonstrated good to moderate activity, and some of those have exhibited more potent activity than etoposide.

ATF2 inhibits ani-tumor effects of BET inhibitor in a negative feedback manner by attenuating ferroptosis

BET inhibitor (BETi) has potential therapeutic effects on human cancer especially in breast cancer. However, the detailed mechanisms remain unclear. Herein, we found that BETi JQ1 and I-BET-151 (I-BET) activated ATF2 through JNK1/2 pathway in breast cancer cells MDA-MB-231 (MB-231). In addition, overexpression of ATF2 blocked the reduction of cell viability induced by JQ1 or I-BET in breast cancer MB-231 and BT-549 cells, cervical cancer HeLa cells and lung cancer A549 cells. The induction of cell death by BETi was also attenuated by ATF2 in MB-231 and BT-549 cells. By contrast, depletion of ATF2 increased cancer cell sensitivity to BETi. In MB-231 cells xenograft model, ATF2 significantly inhibited the anti-tumor effects of JQ1. By detection of the oxidized form gluthione, malondialdehyde and lipid ROS, we showed that overexpression of ATF2 inhibited ferroptosis induced by BETi, whereas depletion of ATF2 promoted ferroptosis by BETi. Furthermore, the underlying mechanisms of ATF2-reduced ferroptosis were investigated. Overexpressed and depleted ATF2 were found to significantly upregulate and downregulate NRF2 protein and mRNA expression, respectively. The significantly positive correlations between NRF2 and ATF2 gene expression were found in breast, lung and cervical cancer tissues from TCGA database. In NRF2-depleted MB-231 cells, ATF2 failed to attenuate JQ1-stimulated ferroptosis. All these results suggested that ATF2 inhibited BETi-induced ferroptosis by increasing NRF2 expression. Altogether, our findings illustrated ATF2 suppressed ani-tumor effects of BETi in a negative feedback manner by attenuating ferroptosis. BETi combined with ATF2 or NRF2 inhibitor might be a novel strategy for treatment of human cancer.

Design and synthesis of novel 1,2,4-Thiadiazole linked imidazo[1,2-b]pyridazine as anticancer agents

A novel series of 1,2,4-thiadiazole linked imidazo[1,2-b]pyridazine (10a-j) derivatives were designed, synthesized and determined for their anticancer activity against various cancer cell lines including breast (MCF-7, MDA MB-231), lung (A549) and prostate (DU-145) by employing MTT assay. The obtained results were expressed in IC50 µM, and etoposide used as reference drug. Among all compounds, 10b, 10c, 10d, 10i and 10j displayed more potent activity. Especially, one compound 10b was possessed most promising activity.

Toll-Iike Receptor-3 Activation Enhances Malignant Traits in Human Breast Cancer Cells Through Hypoxia-inducible Factor-1α.

Hypoxia-inducible factor 1 (HIF1) inhibitors have been proposed as therapeutic agents for several tumor types. HIF1α is induced by hypoxia and by pathogens in normoxia through toll-like receptors (TLRs). The TLR3 activator polyinosinic:polycytidylic acid [poly(I:C)] induces apoptosis in various types of cancer but not in the most aggressive breast cancer cell lines. We hypothesized that the failure of TLR3 stimulation to induce apoptosis in these cells might be due to an elevated HIF1α level and this link might be exploited. Poly(I:C)-induced signaling pathway and expression of HIF1α and HIF1α targets were studied in MDA MB-231 and MCF-7 breast cancer cell lines by western blot. Flow cytometry was used for apoptotic responses and vasculogenic mimicry as bioassay. Poly(I:C) increased expression of HIF1α and its targets BCL2 apoptosis regulator and c-MYC. Moreover, using pharmacological or genetic HIF1 inhibition, reduction of poly(I:C)-induced expression of HIF1α was paralleled by lowering of c-MYC and increased sensitivity to poly(I:C)-induced apoptosis, demonstrating the crucial role of this factor. We provide the first evidence in breast cancer cells that TLR3 stimulation induces HIF1α-dependent vasculogenic mimicry. By using specific inhibitors, we identified a signaling cascade upstream of HIF1α induction. Combined treatment with poly(I:C) and HIF1 inhibitors deserves consideration as an effective strategy in breast cancer therapy.

Radiation and Gold Nanoparticle Increase the Expression of Immunogenic Cell Death Markers in MDA MB 231 Breast Cancer Model

Tumor immunogenic cell death (ICD) plays a major role in stimulating host anti-cancer immune response that can determine the success of cancer radiotherapy (RT). Additionally, ICD can also be induced by radiation itself. The main feature of ICD is the release of immunogenic molecules by dying cells, termed damage associated molecular patterns (DAMPs) that act on innate and adaptive immune components to induce long-lasting antitumor immunity. Two breast cancer (BCa) DAMPs involved in phagocytosis and dendritic cell antigen presentation are Calreticulin (CLR) and HMGB1; loss of HMGB1 expression is linked to poor clinical prognosis. Therefore, these molecules are being studied for their therapeutic and prognostic potential. As RT, either alone or in combination, is often part of standard BCa therapies, the effect of RT and radiosensitizers, such as gold nanoparticles (AuNPs), on DAMPs expression must be considered when designing new protocols, especially if combining RT with an adjuvant mode such as immunotherapy. The goal of this study was to measure the effect of radiation on CLR and HMGB-1 expression in the presence and absence of a novel AuNP radiosensitizer in MDA MB 231 BCa in vitro and in vivo models. We hypothesized that AuNP modulates radiation induced ICD by altering CLR and HMGB1 expression. In vitro: MDA MB 231 cells were incubated for 3h with 14nm AuNPs and irradiated. After 48h and 72h the percentages of CLR and HMGB1 positive cells were determined by flow cytometry. In vivo: Female nude mice bearing MDA MB 231 tumors received intratumoral injections of 14 nm AuNPs. After 24h mice were irradiated with 15 Gy dose using 160 kV photons. Mice were euthanized, histological sections prepared, stained with anti CLR antibodies and analyzed by light microscopy. In vitro, radiation induced increase in the percentages of CLR and HMGB1 positive cells was potentiated by AuNP at 48h and 72h time points. In control cells, AuNP alone increased the percent of HMGB1 positive cells at both time points. The percent of CLR positive cells was increased at 72h only. In vivo, in animals receiving RT or AuNP only, CLR expression was increased relative to control animals and CLR was detected extracellularly after RT, and extra- and intracellularly after AuNP alone. However, after combined RT and AuNP, CLR expression was higher than after single treatments and was detected both, extra- and intracellularly. In BCa patients, induction of ICD may play a critical role in improving clinical outcomes. Here we show that AuNP enhanced the immunogenic effect of a single irradiation dose in BCa cells and mouse model. This effect was measured by an increase in the expression of CLR and HMGB1, DAMPs critical to the response of BCa. In addition, AuNP alone exhibited an immunogenic effect similar to RT alone. These findings support that BCa depends on ICD and provide a platform for designing multimodal BCa RT formulations with novel radiosensitizers or immunotherapy.

Characteristics of Molecularly Engineered Anticancer Drug Conjugated Organic Nanomicelles for Site-Selective Cancer Cell Rupture and Growth Inhibition of Tumor Spheroids.

Site-selective uptake and specific biodistribution of chemotherapeutic drugs are essential prerequisites for targeted cancer therapy. Especially, antibody and peptide conjugated drugs have been attempted as localized therapeutic agents. However, the characteristics of drug conjugated nanosystems are less explored, which are limited with their toxicity, low therapeutic efficacy, complicated synthesis, and high costs. Herein, we report a biocompatible (about 95%) molecularly engineered anticancer drug conjugated nanomicelles (∼200 nm in size) for site-selective CD44 overexpressed cancer cell rupture and tumor growth inhibition. Microscopic analysis demonstrates the distinct visualization of organic-organic interfaces (∼5 nm), which are corroborated with spectroscopic measurements confirmed the conjugation of niclosamide drug with hyaluronic acid (NIC-HA). Uniformly distributed hemocompatible (about 99%) organic nanomicelles exhibit the cellular membrane and cytoplasmic targeting with significant cellular rupture (IC50 of 4 μM for MDA MB 231 cells) indicating their inherent targeting ability for cancer cells and cancer stem cells. An inclusive in vitro and in vivo analysis for targeted antitumor activity (HT1080 tumor xenograft model) of NIC-HA nanoconjugates (∼24.6% loading) exhibited promising cancer cell death and tumor growth inhibition (60%, p < 0.05) due to STAT-3 signaling pathway inhibition and induction of apoptosis in CD44-positive triple negative breast cancer cells.

Fluidic embedding of additional macroporosity in alginate-gelatin composite structure for biomimetic application

Biomimetic characteristics of hydrogel scaffold are tuned in this study utilizing the synergy of alginate, gelatin, and microfluidically embedded voids. Superposition of alginate and gelatin polymer networks results in additional rigidity, which can be tuned by introduction of voids, and thereby allowing faster release of pore pressure through movement of aqueous phase through the pore network. More importantly, voids enabled the cells to penetrate from the surface of seeding into the depth of the scaffold and proliferate there, as demonstrated for MDA MB 231 breast cancer cells. The uniform voids, generated by the microfluidic device, self-align creating uniform macroporosity within the gel structure, get readily filled by the media due to hydrophilicity, and extend the characteristics of composite uniformly across the entire scaffold.

Effect of static magnetic field with quercetin and hesperetin on MCF-7 and MDA MB-231 breast cancer cells

Abstract Objectives Static magnetic field (SMF) was previously in practice for the therapy of some diseases and it has been thought that it may be a reliable supportive technique. The aim of this study was to find out the synergistic effect of SMF administration with flavonoids in terms of apoptosis on breast cancer cell lines. Material and methods The effects of flavonoids on the proliferation of breast cancer cell lines were observed by MTT cell viability test. The cells were treated with SMF + hesperetin and SMF + quercetin. Apoptosis rates and Bax, Bcl-2 protein levels were detected by flow cytometer and Western Blot, respectively. Results Cell lines were treated with quercetin and quercetin + SMF, substantial amount of cells [3.96, 4.86, 11.40% for MCF-7 and MDA MB-231 cell lines, respectively (p&lt;0.001)] were mainly in the apoptotic phase. The apoptosis rates of hesperetin and hesperetin + SMF were 2.53, 6.06, 10.10% (p&lt;0.001) for MCF-7 and MDA MB-231 cell lines, respectively. Bax:Bcl-2 ratios were significantly increased after flavonoids + SMF exposure (2.7 vs. 1.6 fold (p&lt;0.0001) in hesperetin + SMF group and 1.8 vs. 1.3-fold (p&lt;0.0001) in quercetin + SMF group for MCF-7 and MDA MB-231 cell lines, respectively. Conclusions SMF might support the anti-cancer properties of flavonoids, on breast cancer cells via mitochondria-related apoptosis pathway.

Design and synthesis of novel 1-substituted -3-(4-oxo-2-phenylquinazolin-3(4H)-yl) urea and thiourea analogues targeting on TACE, as potent anticancer agents

1-substituted phenyl quinazolinones analogues were designed by performing molecular modelling studies against tumour necrosis factor alpha converting enzyme (TACE PDB Id: 2A8H) and in-silico Lipinski properties for drug likeness. From QSAR studies, it could be concluded that the urea and thiourea groups play a crucial role in enhancing cytotoxic effects of compounds. Substitution of halogens like trifluoromethyl, chloro and allylic functional group may enhance the cytotoxic effect of urea and thiourea analogues. Substitution of phenyl and benzoyl ring were not found effective against cancer. Also, the presence of substituted aromatic ring at position 3 and methyl or thiol group at position 2 are essential for antimicrobial activities of quinazolinone. The synthesized compounds were characterized by TLC, MP, IR, NMR and Mass spectral data and were screened for their anticancer activity. The in vitro anticancer studies were performed on six selected compounds using MTT assay against MDA MB-231 cell line using paclitaxel as a standard. The synthesized 1-substituted -3-(4-oxo-2-phenylquinazolin-3(4h)-yl) urea and thiourea derivatives exhibited significant anticancer activities.

Combine Drug Delivery of Thymoquinone-Doxorubicin by Cockle Shellderived pH-sensitive Aragonite CaCO3 Nanoparticles

Background: Cockleshell-derived aragonite calcium carbonate nanoparticles were prepared by the top-down approach for combine delivery of two types of drugs. Objective: The aim of this study was to synthesize and characterize thymoquinone-doxorubicin loaded cockle shell-derived aragonite calcium carbonate nanoparticle. Aragonite calcium carbonate nanoparticles encapsulating thymoquinone and doxorubicin alone were also prepared. Methods: The blank and drug-loaded nanoparticles were characterized by field emission scanning electron microscopy, transmission electron microscopy, Zeta potential, Fourier transformed infrared and X-ray diffraction. Drug delivery properties, in vitro drug release study at pH 7.4, 6 and 4.8, and effect of blank nanoparticles on MCF10A, 3T3, MDA MB231 cells were also analyzed. Results: The blank and drug-loaded nanoparticles were pleomorphic and their sizes varying from 53.65 ± 10.29 nm to 60.49 ± 11.36 nm with an overall negative charge. The entrapment efficiency of thymoquinone and doxorubicin were 41.6 and 95.8, respectively. The FTIR showed little alteration after loading thymoquinone and doxorubicin while XRD patterns revealed no changes in the crystallizations of nanoparticles after drug loading. The drug release kinetics of doxorubicin and thymoquinone from the nanoparticles showed a continuous and gradual release after an initial burst release was observed. At pH 4.8, about 100% of drug release was noticed, 70% at pH 6 while only 50% at pH 7.4. The cell viability was 80% at a concentration of 1000 ug/ml of blank nanoparticle. Conclusion: The cockle shell-derived pH sensitive aragonite calcium carbonate nanoparticle provides an effective and simple means of multiple drug delivery and function as a platform for pH controlled release of loaded therapeutic agents.

FAM46C/TENT5C functions as a tumor suppressor through inhibition of Plk4 activity

Polo like kinase 4 (Plk4) is a tightly regulated serine threonine kinase that governs centriole duplication. Increased Plk4 expression, which is a feature of many common human cancers, causes centriole overduplication, mitotic irregularities, and chromosomal instability. Plk4 can also promote cancer invasion and metastasis through regulation of the actin cytoskeleton. Herein we demonstrate physical interaction of Plk4 with FAM46C/TENT5C, a conserved protein of unknown function until recently. FAM46C localizes to centrioles, inhibits Plk4 kinase activity, and suppresses Plk4-induced centriole duplication. Interference with Plk4 function by FAM46C was independent of the latter’s nucleotidyl transferase activity. In addition, FAM46C restrained cancer cell invasion and suppressed MDA MB-435 cancer growth in a xenograft model, opposing the effect of Plk4. We demonstrate loss of FAM46C in patient-derived colorectal cancer tumor tissue that becomes more profound with advanced clinical stage. These results implicate FAM46C as a tumor suppressor that acts by inhibiting Plk4 activity.