Anticancer Bioactivity Research Articles

Phytochemical Constituents of Citrus hystrix DC. Leaves Attenuate Inflammation via NF-κB Signaling and NLRP3 Inflammasome Activity in Macrophages.

Citrus hystrix DC. (CH) is found in many countries in Southeast Asia. This plant has been reported for anti-microbial, anti-cancer and anti-inflammatory bioactivities. However, the anti-inflammatory and anti-inflammasome properties of the leaves remain poorly understood. This study aimed to investigate the effect of CH leaves on NLRP3 and NF-κB signaling pathways. CH leaves were sequentially extracted using hexane, ethyl acetate and 95% ethanol to give three crude extracts. An active compound, lupeol was fractionated from the ethanolic extract using chromatographic techniques, and its structure was identified and confirmed by spectroscopic methods. Anti-inflammatory activities were observed on both lipopolysaccharide-stimulated and NLRP3 adenosine triphosphate-induced macrophages. The release of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) was analyzed by Enzyme-Linked Immunosorbent Assay (ELISA). Real-time qRT-polymerase chain reaction (PCR) was used to measure inflammatory-associated gene expression. NF-κB protein expressions were investigated using the immunoblotting technique. The active fraction of ethanolic CH leaves and lupeol significantly reduced the release of pro-inflammatory cytokines and suppressed the expression of both inflammasome genes and NF-κB proteins. The ethanolic extract of CH leaves and lupeol showed potent anti-inflammatory activities by targeting NF-κB and NLRP3 signaling pathways.

Taxonomy, Diversity and Cultivation of the Oudemansielloid/Xeruloid Taxa Hymenopellis, Mucidula, Oudemansiella, and Xerula with Respect to Their Bioactivities: A Review.

The oudemansielloid/xeruloid taxa Hymenopellis, Mucidula, Oudemansiella, and Xerula are genera of Basidiomycota that constitute an important resource of bioactive compounds. Numerous studies have shown antimicrobial, anti-oxidative, anti-cancer, anti-inflammatory and other bioactivities of their extracts. The bioactive principles can be divided into two major groups: (a) hydrophilic polysaccharides with relatively high molecular weights and (b) low molecular medium polar secondary metabolites, such as the antifungal strobilurins. In this review, we summarize the state of the art on biodiversity, cultivation of the fungi and bioactivities of their secondary metabolites and discuss future applications. Although the strobilurins are well-documented, with commercial applications as agrochemical fungicides, there are also other known compounds from this group that have not yet been well-studied. Polysaccharides, dihydro-citrinone phenol A acid, scalusamides, and acetylenic lactones such as xerulin, also have potential applications in the nutraceutical, pharmaceutical and medicinal market and should be further explored. Further studies are recommended to isolate high quality bioactive compounds and fully understand their modes of action. Given that only few species of oudemansielloid/xeruloid mushrooms have been explored for their production of secondary metabolites, these taxa represent unexplored sources of potentially useful and novel bioactive metabolites.

Microfluidic-assisted synthesis and modelling of monodispersed magnetic nanocomposites for biomedical applications

AbstractDroplet microfluidic was devoted to design and fabricate robust devices in the field of biosensing, tissue engineering, drug delivery, cell encapsulation, cell isolation, and lab-on-a-chip. Chitosan was widely used for different biomedical applications because of its unique characteristics such as antibacterial bioactivities, immune-enhancing influences, and anticancer bioactivities. In this research, a model is used for investigating the formation and size of composite droplets in a microfluidic device. The role of the velocity flow ratio in the composite droplet characteristics such as the generation rate and composite droplet size is described. According to the results, a desirable protocol is developed to control the properties of the composite droplets and to compare the size and rate of the composite droplets in a micro device. Furthermore, the level set laminar two-phase flow approach is exploited for studying the composite droplet-breaking procedure. An experimental procedure is used for validation of the simulation process. Various sizes and geometries of the composite droplets are fabricated to depict a potential in biomedical applications such as bioimaging, biosensing, tissue engineering, drug delivery, cell encapsulation, cancer cell isolation, and lab-on-a-chip.

Overexpression of Soybean-Derived Lunasin in Wheat and Assessment of Its Anti-Proliferative Activity in Colorectal Cancer HT-29 Cells.

Lunasin is a soybean-derived peptide that exhibits anticancer bioactivity in different cancer cells and has been identified in different plants. However, recent studies revealed through molecular and chemical analyses that lunasin was absent in wheat and other cereals. In this study, the soybean-derived lunasin was cloned into pCAMBIA3300 and we transferred the expression vector into wheat via an Agrobacterium-mediated transformation. The identification of transgenic wheat was detected by polymerase chain reaction, Western blot analysis, and ultra-performance liquid chromatography with tandem mass spectrometry. An enzyme-linked immunosorbent assay showed that lunasin content in transgenic wheat L32-3, L32-6, and L33-1 was 308.63, 436.78, and 349.07 µg/g, respectively, while lunasin was not detected in wild-type wheat. Lunasin enrichment from transgenic wheat displayed an increased anti-proliferative activity compared with peptide enrichment from wild-type wheat in HT-29 cells. Moreover, the results of a real-time quantitative polymerase chain reaction showed a significant elevation in p21, Bax, and caspase-3 expression, while Bcl-2 was significantly downregulated. In conclusion, soybean-derived lunasin was successfully expressed in wheat via Agrobacterium-mediated transformation and may exert anti-proliferative activity by regulating the apoptosis pathway in HT-29 cells, which provides an effective approach to compensate for the absence of lunasin in wheat.

Jasmonates induce Arabidopsis bioactivities selectively inhibiting the growth of breast cancer cells through CDC6 and mTOR.

Summary Phytochemicals are used often in vitro and in vivo in cancer research. The plant hormones jasmonates (JAs) control the synthesis of specialized metabolites through complex regulatory networks. JAs possess selective cytotoxicity in mixed populations of cancer and normal cells.Here, direct incubation of leaf explants from the non‐medicinal plant Arabidopsis thaliana with human breast cancer cells, selectively suppresses cancer cell growth. High‐throughput LC‐MS identified Arabidopsis metabolites. Protein and transcript levels of cell cycle regulators were examined in breast cancer cells.A synergistic effect by methyljasmonate (MeJA) and by compounds upregulated in the metabolome of MeJA‐treated Arabidopsis leaves, on the breast cancer cell cycle, is associated with Cell Division Cycle 6 (CDC6), Cyclin‐dependent kinase 2 (CDK2), Cyclins D1 and D3, indicating that key cell cycle components mediate cell viability reduction. Bioactives such as indoles, quinolines and cis‐(+)‐12‐oxophytodienoic acid, in synergy, could act as anticancer compounds.Our work suggests a universal role for MeJA‐treatment of Arabidopsis in altering the DNA replication regulator CDC6, supporting conservation, across kingdoms, of cell cycle regulation, through the crosstalk between the mechanistic target of rapamycin, mTOR and JAs. This study has important implications for the identification of metabolites with anti‐cancer bioactivities in plants with no known medicinal pedigree and it will have applications in developing disease treatments

Studi In Silico Bioaktivitas Antikanker Senyawa Aktif Dalam Minyak Biji Buah Wali [Brucea javanica (L.) Merr

Insilico study of anticancer bioactivity in oil of “buah wali” [Brucea javanica (L.) Merr] has been successfully carried out. “Buah Wali” (Brucea javanica (L.) Merr) is known to treat various diseases such as diabetes, diarrhea, and malaria. In addition, “buah wali” seeds are supported to have antidiabetic, antioxidant, and anticancer activities. The stages of the study began by taking a sample of “buah wali”seeds, then extracted to get oil of “buah wali”. While GC-MS analysis resulted Octadec-9-enoic acid (56.25%), palmitic acid (13.82%), stearic acid (10.57%), and acids -9-octadecanoate (5.91%) were found as the major components of the seed oil. Based on these compounds, docking molecular was carried out to find anticancer bioactivity. The results obtained are compounds that have lower binding energy than the native ligands [Octadec-9-enoic acid (-72.4518), hexadecanoic acid (-70.2136), octadecanoic (-72.2362).

Isolation, characterization, in vitro anticancer activity, dft calculations, molecular docking, bioactivity score, drug-likeness and admet studies of eight phytoconstituents from brown alga sargassum platycarpum

Recently, macroalgae or seaweeds serve as a treasure of potential drugs for cancer therapy. The present study investigated the cytotoxic activity of eight compounds isolated from the brown alga Sargassum platycarpum for the first time. These isolates were identified as hexadecanoic acid (1), oleic acid (2), saringosterol (3 and 4, 1:1 mixture of C-24epimers), β-sitosterol (5), glycoglycerolipid (6), loliolide (7) and Kjellmanianone (8) by spectroscopic techniques. Two epimers of saringosterol, (24-R)-saringosterol (3) and (24-S)-saringosterol (4), were subsequently separated by HPLC. (24-S)-saringosterol (4) and (24-R)-saringosterol (3) exhibited potent cytotoxicity against HepG-2 cells with IC50 of 0.10±0.00 and 0.11±0.00 µM, respectively with compared to standard 5-Fluorouracil (IC50 of 0.63±0.28 µM) and other isolates. MEP, EHOMO, ELUMO and global properties of all isolated compounds are computed by DFT methods. Molecular docking study showed that most of the isolated compounds especially compounds 3 and 4 interact strongly with 4PYP with the highest binding energies maintained that the high cytotoxic activity of these compounds against HepG-2 cells in the experimental part. Bioactivity Score, Drug-Likeness and ADMET studies supported the potential biological activities of most isolated compounds especially compounds 3 and 4 and also created attention for developing them to act as good candidates.

The Potential of Phytochemicals in Oral Cancer Prevention and Therapy: A Review of the Evidence.

The etiological factors of oral cancer are complex including drinking alcohol, smoking tobacco, betel quid chewing, human papillomavirus infection, and nutritional deficiencies. Understanding the molecular mechanism of oral cancer is vital. The traditional treatment for patients with oral squamous cell carcinoma (e.g., surgery, radiotherapy, and chemotherapy) and targeted molecular therapy still have numerous shortcomings. In recent years, the use of phytochemical factors to prevent or treat cancer has received increasing attention. These phytochemicals have little or no toxicity against healthy tissues and are thus ideal chemopreventive agents. However, phytochemicals usually have low water solubility, low bioavailability, and insufficient targeting which limit therapeutic use. Numerous studies have investigated the development of phytochemical delivery systems to address these problems. The present article provides an overview of oral cancer including the etiological factors, diagnosis, and traditional therapy. Furthermore, the classification, dietary sources, anticancer bioactivity, delivery system improvements, and molecular mechanisms against oral cancer of phytochemicals are also discussed in this review.

Integrated Array Chip for High-Throughput Screening of Species Differences in Metabolism.

Species differences in metabolism may produce failure prediction of drug efficacy/toxicity in humans. Integration of metabolic competence and cellular effect assays in vitro can provide insight into the species differences in metabolism; however, a co-culture platform with features of high throughput, operational simplicity, low sample consumption, and independent layouts is required for potential usage in industrial test settings. Herein, we developed an integrated array chip (IAC) to evaluate the species differences in metabolism through metabolism-induced anticancer bioactivity as a case. The IAC consisted of two functional parts: a micropillar chip for immobilization of liver microsomes and a microwell chip for three-dimensional (3D) tumor cell culture. First, optimized parameters of the micropillar chip for microsomal encapsulation were obtained by cross-shaped protrusions and a 2.5 μL volume of 3D agarose spots. Next, we examined factors influencing metabolism-induced anticancer bioactivity. Feasibility of the IAC was validated by four model prodrugs using image-based bioactivity detection and mass spectrometry (MS)-based metabolite analysis. Finally, a species-specific IAC was used for selection of animal species that best resembles metabolism-induced drug response to humans at throughputs. Overall, the IAC provides a promising co-culture platform for identifying species differences in metabolism and selection of animal models to accelerate drug discovery.

Biological Activity of Humulus Lupulus (L.) Essential Oil and Its Main Components Against Sitophilus granarius (L.).

Besides its use in the brewing industry, hop cones appear as a powerful source of biologically active compounds, already checked for their putative anticancer, antimicrobial, and other bioactivities. Conversely, hop use in pest control remains to date under-investigated. Therefore, the biological activity of hop essential oil (EO) and its main constituents was investigated here against Sitophilus granarius. Adult contact toxicity was found 24 h after treatment with hop EO (LD50/LD90 13.30/40.23 µg/adult), and its three most abundant components, α-humulene, β-myrcene, and β-caryophyllene (LD50/LD90 41.87/73.51, 75.91/126.05, and 138.51/241.27 µg/adult, respectively); negligible variations at 48 h, except for α-humulene (LD50/LD90 26.83/49.49 µg/adult), were found. The fumigant toxicity of the EO and terpenes was also checked: in the absence of wheat grains, β-myrcene showed the highest inhalation toxicity (LC50/LC90 72.78/116.92 mg/L air), whereas α-humulene, β-caryophyllene, and the EO induced similar values (LC50/LC90 about 130/200 mg/L air); with the exception for EO, the wheat presence increased (30–50%) LC50/LC90 values. Moreover, EO and terpenes were perceived by insect antennae and elicited repellent activity. Only β-caryophyllene showed an anticholinesterase effect, this suggesting that different mechanisms of action should be responsible for hop EO toxicity. Therefore, hop EO appears suitable for developing control means against this pest.

Calcium Phosphate Mineralized Black Phosphorous with Enhanced Functionality and Anticancer Bioactivity

AbstractBiodegradable inorganic nanomaterials have opened new perspectives for cancer therapy due to their inherent anticancer activity. Black phosphorus nanosheets (BPs) with their unique bioactivity have recently been identified as promising cancer therapeutic agents but their application is hampered by the difficulty in surface functionalization. Herein, an in situ calcium phosphate (CaP) mineralization strategy is described to enhance the anticancer activity of BPs. By using BPs as the phosphate sources and growth templates, the synthesized CaP‐mineralized BPs (CaBPs) retain the intrinsic properties of BPs and at the same time have high loading capacities for various fluorophores to enable effective bioimaging and tracing. Compared to BPs, CaBPs exhibit enhanced and selective anticancer bioactivity due to the improved pH‐responsive degradation behavior and intracellular Ca2+ overloading in cancer cells. Furthermore, CaBPs specifically target mitochondria and cause structural damage, thus leading to mitochondria‐mediated apoptosis in cancer cells. After intravenous injection, CaBPs target orthotopic breast cancer cells to inhibit tumor growth without giving rise to adverse effects or toxicity. The results demonstrate the great potential of CaBPs as targeted anticancer agents and the CaP mineralization approach provides a versatile surface functionalization strategy for nanotherapeutic agents.

Direct targeting of HSP90 with daurisoline destabilizes β-catenin to suppress lung cancer tumorigenesis.

Lung cancer is the most frequent cancer worldwide with a poor prognosis. Identification of novel cancer targets and useful therapeutic strategies without toxicity are urgently needed. In this study, we screened natural products for anticancer bioactivity in a library consisting of 429 small molecules. We demonstrated for the first time that daurisoline, a constituent of Rhizoma Menispermi, repressed lung cancer cell proliferation by inducing cell cycle arrest at the G1 phase. Furthermore, daurisoline was found not only to suppress the growth of lung tumor xenografts in animals without obvious side effects, but also to inhibit cell migration and invasion. Mechanistically, quantitative proteomics and bioinformatics analyses, Western blotting and qRT-PCR confirmed that daurisoline exerted its anticancer effects by inhibiting the expression levels of β-catenin and its downstream targets c-myc and cyclin D1. Furthermore, our data from Drug Affinity Responsive Target Stability (DARTS), isothermal titration calorimetry (ITC) and a series of functional assays demonstrated that daurisoline could target HSP90 directly and disrupt its interaction with β-catenin, therefore increasing the ubiquitin-mediated proteasomal degradation of β-catenin. This study reveals that daurisoline could be a promising therapeutic strategy for the treatment of lung cancer.

Shikonin relieves osteoporosis of ovariectomized mice by inhibiting RANKL-induced NF-κB and NFAT pathways

Postmenopausal osteoporosis is very common in women. Currently, many kinds of new drugs are being developed for this disease. Postmenopausal osteoporosis is closely related to overactivity of osteoclasts in body. Shikonin is purple red naphthoquinone pigment extracted from lithospermum, which has anti-inflammation, antivirus, anticancer and other bioactivities. At the same time, it has been proved that shikonin can promote the proliferation and differentiation of osteoblasts, but its influence on osteoclasts and molecular mechanism are unknown. Our study showed that shikonin could inhibit the activity and formation of RANKL-mediated osteoclasts depending on dose without affecting the activity of bone marrow macrophages (BMM). In addition, we have also found that shikonin can inhibit the expression of specific marker gene of osteoclasts, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cathepsin K (Ctsk), tartrate resistant acid phosphatase (TRAcP) and calcitonin receptor. Shikonin also could promote the proliferation of MC3T3-E1, increasing the expression of mRNA related to osteogenesis, like the expression of bone morphogenetic protein-2 (BMP-2), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). Luciferase reporter gene assay and Western blot analysis further indicated that shikonin could inhibit the activity of RANKL-induced NF-κB and NFAT receptors. Moreover, shikonin can also slow down bone loss of ovariectomized (OVX) mice by inhibiting the activity of osteoclasts. This work explains the molecular mechanism of shikonin in RANKL-mediated formation of osteoclasts, and reveals the potential of further developing shikonin into a new drug for prevention and treatment of postmenopausal osteoporosis.

Ultrasound-Assisted Enzymatic Extraction of Adenosine from Vietnamese Cordyceps militaris and Bioactivity Analysis of the Extract

Vietnamese Cordyceps militaris (C. militaris) has long been recognized as one of the most valuable traditional Chinese medicines. In this study, adenosine was extracted from Vietnamese C. militaris by ultrasound-assisted enzymatic extraction method (UAEE) using water as a solvent. Then, the effects of five single factors on adenosine content including pH, enzyme-to-material ratio, ultrasonic power, ultrasonic time, and ultrasonic temperature were determined. After that, three factors consisting of ultrasonic power, ultrasonic time, and ultrasonic temperature were chosen based on their effects on adenosine content. The simultaneous influence of these factors on the adenosine content was investigated by response surface method using central composite design. The adenosine content was evaluated by high-performance liquid chromatography method. Under the optimal conditions, the extract was evaluated for antioxidant and anticancer bioactivities. In addition, different extraction methods including aqueous extraction (AE), ultrasound-assisted extraction (UAE), and enzyme-assisted extraction (EAE) methods were carried out to compare with UAEE. As a result, it can be concluded that UAEE is a promising method for adenosine extraction and further studies regarding isolation and purification need to be conducted.

Natural and grafted cyclotides in cancer therapy: An insight.

Cyclotides is a rapidly growing class of plant-derived cyclic peptides exhibiting several bioactivities with potential applications in the agricultural and pharmaceutical sectors. Both natural and grafted cyclotides have shown promise in cancer therapy. Approximately 70 natural cyclotides belonging to three plant families (Fabaceae, Rubiaceae, and Violaceae) have shown cytotoxicity against several cancer cell lines. Cyclotides exhibit considerable stability against thermal and enzymatic proteolysis, owing to their unique structure with knotted topology and head to tail cyclization. Further, their small size, high stability, oral bioavailability, and tolerance to amino acid substitution in structural loops make them an ideal platform for designing peptide-based drugs for cancer. Thus, cyclotides provide ideal scaffolds for bioactive epitope grafting and facilitating drug delivery in cancer treatment. Many anticancer linear peptides have been grafted in cysteine knotted cyclic framework of cyclotide for enhancing their cell permeability across cellular membranes, thereby improving their delivery and pharmacokinetics. The present review comprehensively discusses the distribution, toxicity, and anticancer bioactivity of natural cyclotides. Further, it systematically elaborates on the role and action of epitopes' into grafted cyclotides in targeting cancer. The review also encompasses related patents landscape study and future challenges in peptide-based cancer therapy.

Bioactivity Guided Fractionation and Elucidation of Anti-Cancer Properties of Imperata Cylindrica Leaf Extracts

Background:In our earlier study, we reported the anticancer effect of methanolic extracts of, I. cylindrica leaf (ICL) against human oral squamous cell carcinoma cell lines SCC-9. The cytotoxic effect of ICL methanolic extract was specific to the cancer cells and not to the normal cells. The present study aimed to fractionate the ICL methanolic extract to derive anticancer bioactives. Methods:The ICL methanolic extract was subjected to a bioactivity guided fractionation. Cytotoxic, cell cycle inhibitory, apoptosis and caspase gene expression inducing activity of the active fractions were evaluated using MTT assay, FACS analysis, Annexin V binding assay and RT-PCR respectively. Results:The hexane fraction of ICL methanolic extract (ICLH) was observed to be the most bioactive fraction. It was shown to possess effective cytotoxic and cell cycle inhibitory activities against SCC-9 cells. The hexane fraction also induced apoptosis in SCC-9 cells which was further established at the level of caspase 3 and 8 gene expressions. Conclusion:Overall, the results clearly establish the potential of ICLH extract to inhibit cell proliferation and induce apoptosis in the SCC-9 cells. Further analysis of the ICLH fraction could result in development of effective anticancer therapeutics. The natural abundance of I. cylindrica with its wide geographic distribution could make it a preferred natural resource for obtaining novel, cost-effective, anticancer therapeutics with minimal systemic side effects.

Bioactive Anti-inflammatory, Antibacterial, Antioxidative Silicon-Based Nanofibrous Dressing Enables Cutaneous Tumor Photothermo-Chemo Therapy and Infection-Induced Wound Healing.

Traditional skin tumor surgery and chronic bacterial-infection-induced wound healing/skin regeneration is still a challenge. The ideal strategy should eliminate the tumor, enhance wound healing/skin formation, and be anti-infection. Herein, we designed a multifunctional elastomeric poly(l-lactic acid)-poly(citrate siloxane)-curcumin@polydopamine hybrid nanofibrous scaffold (denoted as PPCP matrix) for tumor-infection therapy and infection-induced wound healing. The PPCP matrix showed intrinsically multifunctional properties including antioxidative, anti-inflammatory, photothermal, antibacterial, anticancer, and angiogenesis bioactivities. The polydopamine/curcumin presented an excellent near-infrared photothermal/cancer cell toxicity capacity, respectively, which supported PPCP for synergetic skin tumor therapy and antibacterial properties in vitro/in vivo. Additionally, the PPCP nanofibrous matrix significantly promotes the adhesion and proliferation of normal skin cells and accelerates the cutaneous wound healing in normal mice and bacterial-infected mice by enhancing the early angiogenesis. The PPCP nanofibrous matrix with multifunctional bioactivities provides a competitive strategy for skin tumor and bacterial-infection-induced wound healing.

Antiproliferative Activity of Olive Extract Rich in Polyphenols and Modified Pectin on Bladder Cancer Cells.

Bladder cancer (BC) is one of the most common human cancers. There is an interest in controlling and treating BC and other types of cancer via the use of natural substances and/or combination chemotherapy. Modified forms of pectin have been reported to possess anticancer bioactivity related to the interaction of galactosyl, a main component of pectin, with galectin-3, a carbohydrate-binding protein that is overexpressed on many types of cancer cells. In this study, the antiproliferative effect on BC of novel modified pectins extracted from olives was evaluated. Pectoliv extracts, with high polyphenol content associated to polysaccharides rich in pectin, exhibited an important antiproliferative capacity in vitro against four human BC cells lines, RT112, T24, J82, and SCaBER. Pectoliv treatment reduced the expression of galectin-1 and galectin-3 and significantly inhibited the agglutination of erythrocytes. Thus, Pectoliv may have the potential for development as a novel galectin-3 inhibitor.

Biochemical activities of new isatin derivative against WiDr colon cancer

One of the harmful cancer and the major contributors to deaths is colon cancer. Isatin and its derivatives are widely studied for pharmacological activity. Some isatin compounds with pyrrole, halogen, and hydroxyl substituents have anticancer bioactivity. In the present work, a new isatin derivative, 5-fluoro-3-hydroxy-3-(1H-pyrrole-2-yl)indolin-2-one, has been successfully synthesized with a yield of 66%. The aim of this study is to test the compound cytotoxicity against WiDr colon cancer cells. The cell viability was determined through MTT assay using the ELISA reader instruments. Bioactivity test revealed that 5-fluoro-3-hydroxy-3-(1H-pyrrole-2-yl) indolin-2-one was cytotoxic against WiDr colon cancer cells IC50 for 410 μg/ml.

An integrated biomimetic array chip for high-throughput co-culture of liver and tumor microtissues for advanced anticancer bioactivity screening.

The integration of liver metabolism and hepatotoxicity evaluation for anticancer bioactivity assays in vitro is of fundamental importance to better predict the efficacy and safety of anticancer drugs. In particular, there is a lack of co-culture techniques that can fully mimic the physiological microenvironment at speeds consistent with high-throughput screening. Herein, an integrated Biomimetic Array Chip (iBAC) that enables co-culture of three-dimensional (3D) liver and tumor microtissues was developed for advanced anticancer bioactivity screening at throughputs. The iBAC consisted of two functional chips, a liver chip and a tumor chip containing a cross-shaped protrusion on the tip of a pillar array for co-culture. First, the 3D biomimetic liver microtissue on the liver chip was optimized to mimic superior liver function. Next, the constructed iBAC was evaluated for metabolism-induced anticancer bioactivity by using model prodrugs and for the effect of drug-drug interactions. Finally, the functionality of the iBAC for simultaneous evaluation of anticancer bioactivity and hepatotoxicity was verified. The iBAC exhibits superior performance in biomimetic and integrated functions as well as operationally simple and high-throughput co-culture that makes a good balance between functionality and throughput. Overall, the iBAC provides an integrated, biomimetic and high-throughput co-culture platform to complement the conventional bioactivity assay in tiered screening strategies and could be used as a secondary screening tool at the early phase of drug development.