Effects of Metallic and Carbon-Based Nanomaterials on Human Pancreatic Cancer Cell Lines AsPC-1 and BxPC-3

Pancreatic cancer, due to its asymptomatic development and drug-resistance, is difficult to cure. As many metallic and carbon-based nanomaterials have shown anticancer properties, we decided to investigate their potential use as anticancer agents against human pancreatic adenocarcinoma. The objective of the study was to evaluate the toxic properties of the following nanomaterials: silver (Ag), gold (Au), platinum (Pt), graphene oxide (GO), diamond (ND), and fullerenol (C₆₀(OH)₄₀) against the cell lines BxPC-3, AsPC-1, HFFF-2, and HS-5. The potential cytotoxic properties were evaluated by the assessment of the cell morphology, cell viability, and cell membrane damage. The cancer cell responses to GO and ND were analysed by determination of changes in the levels of 40 different pro-inflammatory proteins. Our studies revealed that the highest cytotoxicity was obtained after the ND treatment. Moreover, BxPC-3 cells were more sensitive to ND than AsPC-1 cells due to the ND-induced ROS production. Furthermore, in both of the cancer cell lines, ND caused an increased level of IL-8 and a decreased level of TIMP-2, whereas GO caused only decreased levels of TIMP-2 and ICAM-1 proteins. This work provides important data on the toxicity of various nanoparticles against pancreatic adenocarcinoma cell lines.     

Tropinone-Derived Alkaloids as Potent Anticancer Agents: Synthesis,Tyrosinase Inhibition,Mechanism of Action,DFT Calculation,and Molecular Docking Studies

A new series of hybrid compounds with tropinone and thiazole rings in the structure was designed and synthesized as potential anticancer agents. They were tested against human multiple myeloma (RPMI 8226), lung carcinoma (A549), breast adenocarcinoma (MDA-MB-231), and mouse skin melanoma (B16-F10) cell lines. Toxicity was tested on human normal skin fibroblasts (HSF) and normal colon fibroblasts (CCD-18Co). The growth inhibition mechanism of the most active derivative was analyzed through investigation of its effect on the distribution of cell cycle phases and ability to induce apoptosis and necrosis in RPMI 8226 and A549 cancer cells. The tyrosinase inhibitory potential was assessed, followed by molecular docking studies. Compounds 3a–3h show high anticancer activity against MDA-MB-231 and B16-F10 cell lines with IC₅₀ values of 1.51–3.03 µM. Moreover, the cytotoxic activity of the investigated compounds against HSF and CCD-18Co cells was 8–70 times lower than against the cancer cells or no toxicity was shown in our tests, with derivative 3a being particularly successful. The mechanism of action of compound 3a in RPMI 8226 cell was shown to be through induction of cell death through apoptosis. The derivatives show ability to inhibit the tyrosinase activity with a mixed mechanism of inhibition. The final molecular docking results showed for IC₅₀ distinct correlation with experiment.     

Sasa quelpaertensis Leaf Extract Inhibits Colon Cancer by Regulating Cancer Cell Stemness in Vitro and in Vivo

A rare subpopulation of cancer cells, termed cancer stem cells (CSCs), may be responsible for tumor relapse and resistance to conventional chemotherapy. The development of a non-toxic, natural treatment for the elimination of CSCs is considered a strategy for cancer treatment with minimal side effects. In the present study, the potential for Sasa quelpaertensis leaf extract (SQE) and its two bioactive compounds, tricin and p-coumaric acid, to exert anti-CSC effects by suppressing cancer stemness characteristics were evaluated in colon cancer cells. CD133⁺CD44⁺ cells were isolated from HT29 and HCT116 cell lines using flow-activated cell sorting (FACs). SQE treatment was found to significantly suppress the self-renewal capacity of both cell lines. SQE treatment was also associated with the down-regulation of β-catenin and phosphorylated GSK3β, while significantly enhancing cell differentiation by up-regulating CK20 expression and blocking the expression of several stem cell markers, including DLK1, Notch1, and Sox-2. In vivo, SQE supplementation suppressed tumor growth in a xenograft model by down-regulating stem cell markers and β-catenin as well as HIF-1α signaling. Compared with two bioactive compounds of SQE, SQE exhibited the most effective anti-CSC properties. Taken together, these results provide evidence that SQE inhibits colon cancer by regulating the characteristics of CSCs.     

Synthesis of Tamoxifen-Artemisinin and Estrogen-Artemisinin Hybrids Highly Potent Against Breast and Prostate Cancer

In the search for new and effective treatments of breast and prostate cancer, a series of hybrid compounds based on tamoxifen, estrogens, and artemisinin were successfully synthesized and analyzed for their in vitro activities against human prostate (PC-3) and breast cancer (MCF-7) cell lines. Most of the hybrid compounds exhibit a strong anticancer activity against both cancer cell lines – for example, EC₅₀ (PC-3) down to 1.07 μM, and EC₅₀ (MCF-7) down to 2.08 μM – thus showing higher activities than their parent compounds 4-hydroxytamoxifen (afimoxifene, 7 ; EC₅₀=75.1 (PC-3) and 19.3 μM (MCF-7)), dihydroartemisinin ( 2 ; EC₅₀=263.6 (PC-3) and 49.3 μM (MCF-7)), and artesunic acid ( 3 ; EC₅₀=195.1 (PC-3) and 32.0 μM (MCF-7)). The most potent compounds were the estrogen-artemisinin hybrids 27 and 28 (EC₅₀=1.18 and 1.07 μM, respectively) against prostate cancer, and hybrid 23 (EC₅₀=2.08 μM) against breast cancer. These findings demonstrate the high potential of hybridization of artemisinin and estrogens to further improve their anticancer activities and to produce synergistic effects between linked pharmacophores.     

One-Pot Three-Component Synthesis of Novel Diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(arylamino)methyl)phosphonate as Potential Anticancer Agents

With the aim of discovering new anticancer agents, we have designed and synthesized novel α-aminophosphonate derivatives containing a 2-oxoquinoline structure using a convenient one-pot three-component method. The newly synthesized compounds were evaluated for antitumor activities against the A549 (human lung adenocarcinoma cell), HeLa (human cervical carcinoma cell), MCF-7 (human breast cancer cell), and U2OS (human osteosarcoma cell) cancer cell lines in vitro, employing a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The results of pharmacological screening indicated that many compounds exhibited moderate to high levels of antitumor activities against the tested cancer cell lines and that most compounds showed more potent inhibitory activities comparable to 5-fluorouracil (5-FU) which was used as a positive control. The mechanism of representative compound 4u (diethyl((2-oxo-1,2-dihydroquinolin-3-yl)(phenyl-amino)methyl)phosphonate) indicated that the compound mainly arrested HeLa cells in S and G2 stages and was accompanied by apoptosis in HeLa cells. This action was confirmed by acridine orange/ethidium bromide staining, Hoechst 33342 staining, and flow cytometry.     

Synthesis and antitumor activity of 3-(2-phenyl-1,3-thiazol-4-yl)-1H-indoles and 3-(2-phenyl-1,3-thiazol-4-yl)-1H-7-azaindoles

Given the potent antimicrobial, antiviral, and antitumor activities of many natural products, there is an increasing interest in the synthesis of new molecules based on natural compound scaffolds. Based on a 2,4-bis(3'-indolyl)imidazole skeleton, two new series of phenylthiazolylindoles and phenylthiazolyl-7-azaindoles were obtained by Hantzsch reaction between substituted phenylthioamides and the α-bromoacetyl derivatives. Some azaindole derivatives, tested at the National Cancer Institute against a panel of ～60 tumor cell lines derived from nine human cancer cell types, showed inhibitory effects against all cell lines investigated at micromolar to nanomolar concentrations. Two of them exhibited a high affinity for CDK1, with IC(50) values of 0.41 and 0.85 μM. These promising results will set the foundation for future investigations into the development of anticancer therapies.     

Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking

In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds 6b,d–g, and 7b showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound 6e displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, 6e was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound 6e endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.     

Cytotoxic Potential of a-Azepano- and 3-Amino-3,4-SeCo-Triterpenoids

Semi-synthetic triterpenoids, holding an amino substituted seven-membered A-ring (azepano-ring), which could be synthesized from triterpenic oximes through a Beckmann type rearrangement followed by a reduction of lactame fragment, are considered to be novel promising agents exhibiting anti-microbial, alpha-glucosidase, and butyrylcholinesterase inhibitory activities. In this study, in an attempt to develop new antitumor candidates, a series of A-ring azepano- and 3-amino-3,4-seco-derivatives of betulin, oleanolic, ursolic, and glycyrrhetinic acids were evaluated for their cytotoxic activity against five human cancer cell lines and non-malignant mouse fibroblasts by means of a colorimetric sulforhodamine assay. Azepanoallobetulinic acid amide derivative 11 was the most cytotoxic compound of this series but showed little selectivity between the different human tumor cell lines. Flow cytometry experiments showed compound 11 to act mainly by apoptosis (44.3%) and late apoptosis (21.4%). The compounds were further screened at the National Cancer Institute towards a panel of 60 cancer cell lines. It was found that compounds 3, 4, 7, 8, 9, 11, 15, 16, 19, and 20 showed growth inhibitory (GI₅₀) against the most sensitive cell lines at submicromolar concentrations (0.20–0.94 μM), and their cytotoxic activity (LC₅₀) was also high (1–6 μM). Derivatives 3, 8, 11, 15, and 16 demonstrated a certain selectivity profile at GI₅₀ level from 5.16 to 9.56 towards K-562, CCRF-CEM, HL-60(TB), and RPMI-8226 (Leukemia), HT29 (Colon cancer), and OVCAR-4 (Ovarian cancer) cell lines. Selectivity indexes of azepanoerythrodiol 3 at TGI level ranged from 5.93 (CNS cancer cell lines SF-539, SNB-19 and SNB-75) to 14.89 for HCT-116 (colon cancer) with SI 9.56 at GI₅₀ level for the leukemia cell line K-562. The present study highlighted the importance of A-azepano-ring in the triterpenic core for the development of novel antitumor agents, and a future aim to increase the selectivity profile will thus lie in the area of modifications of azepano-triterpenic acids at their carboxyl group.     

Novel N-Substituted Amino Acid Hydrazone-Isatin Derivatives: Synthesis,Antioxidant Activity,and Anticancer Activity in 2D and 3D Models In Vitro

A series of novel mono and bishydrazones each bearing a 2-oxindole moiety along with substituted phenylaminopropanamide, pyrrolidin-2-one, benzimidazole, diphenylmethane, or diphenylamine fragments were synthesized, and their anticancer activities were tested by MTT assay against human melanoma A375 and colon adenocarcinoma HT-29 cell lines. In general, the synthesized compounds were more cytotoxic against HT-29 than A375. 3-((4-Methoxyphenyl)(3-oxo-3-(2-(2-oxoindolin-3-ylidene)hydrazinyl)propyl)amino)-N′-(2-oxoindolin-3-ylidene)propanehydrazide and (N′,N‴)-1,1′-(methylenebis(4,1-phenylene))bis(5-oxo-N′-(2-oxoindolin-3-ylidene)pyrrolidine-3-carbohydrazide) were identified as the most active compounds against HT-29 in 2D and 3D cell cultures. The same compounds showed the highest antioxidant activity among the synthesized compounds screened by ferric reducing antioxidant power assay (FRAP). Their antioxidant activity is on par with that of a well-known antioxidant ascorbic acid.     

The Role of Sialyl-Tn in Cancer

Activation of an aberrant glycosylation pathway in cancer cells can lead to expression of the onco-foetal sialyl-Tn (sTn) antigen. STn is a truncated O-glycan containing a sialic acid α-2,6 linked to GalNAc α-O-Ser/Thr and is associated with an adverse outcome and poor prognosis in cancer patients. The biosynthesis of the sTn antigen has been linked to the expression of the sialytransferase ST6GalNAc1, and also to mutations in and loss of heterozygosity of the COSMC gene. sTn neo- or over-expression occurs in many types of epithelial cancer including gastric, colon, breast, lung, oesophageal, prostate and endometrial cancer. sTn is believed to be carried by a variety of glycoproteins and may influence protein function and be involved in tumour development. This review discusses how the role of sTn in cancer development and tumour cell invasiveness might be organ specific and occur through different mechanisms depending on each cancer type or subtype. As the sTn-antigen is expressed early in carcinogenesis targeting sTn in cancer may enable the targeting of tumours from the earliest stage.     

Design and Synthesis of Aminostilbene–Arylpropenones as Tubulin Polymerization Inhibitors

A series of aminostilbene—arylpropenones were designed and synthesized by Michael addition and were investigated for their cytotoxic activity against various human cancer cell lines. Some of the investigated compounds exhibited significant antiproliferative activity against a panel of 60 human cancer cell lines of the US National Cancer Institute, with 50 % growth inhibition (GI₅₀) values in the range from <0.01 to 19.9 μM . One of the compounds showed a broad spectrum of antiproliferative efficacy on most of the cell lines, with a GI₅₀ value of <0.01 μM . All of the synthesized compounds displayed cytotoxicity against A549 (non‐small‐cell lung cancer), HeLa (cervical carcinoma), MCF‐7 (breast cancer), and HCT116 (colon carcinoma) with 50 % inhibitory concentration (IC₅₀) values ranging from 0.011 to 8.56 μM . A cell cycle assay revealed that these compounds arrested the G2/M phase of the cell cycle. Two compounds exhibited strong inhibitory effects on tubulin assembly with IC₅₀ values of 0.71 and 0.79 μM . Moreover, dot‐blot analysis of cyclin B1 demonstrated that some of the congeners strongly induced cyclin B1 protein levels. Molecular docking studies indicated that these compounds occupy the colchicine binding site of tubulin.     

Increased Preventive Effect on Colon Carcinogenesis by Use of Resistant Starch (RS3) as the Carrier for Polysaccharide of Larimichthys Crocea Swimming Bladder

The preventive effect of polysaccharide of Larimichthys crocea swimming bladder (PLCSB) and the increase of this effect by use of resistant starch (RS3) as the carrier for PLCSB on azoxymethane (AOM) and dextran sulfate sodium (DSS)-inducing colon carcinogenesis in C57BL/6 mice has been studied. RS3 microspheres carrying PLCSB (RS3 + PLCSB) were produced and evaluated as a potentially improved colon carcinogenesis therapy for this study. The body weight, colon length, and colon weight of mice were determined, and colonic tissues were histologically observed. The serum levels of proinflammatory cytokines and the inflammation and apoptosis-related genes in colonic tissue were also tested. The PLCSB or RS3 + PLCSB significantly suppressed AOM and DSS-induced body weight loss, colon length shortening and decreased the colon weight to length ratio. PLCSB or RS3 + PLCSB reduced the levels of the serum pro-inflammatory cytokines IL-6, IL-12, TNF-α, and IFN-γ to a greater extent compared with the control mice, and the levels of RS3 + PLCSB were more close to the normal mice than PLCSB treated mice. Histopathological examination of sections of colon tissues showed that the RS3 + PLCSB group recovered well from colon carcinogenesis; however, the tissue sections of the stachyose + starch could reduce the necrosis degree. PLCSB significantly induced apoptosis in tissues of mice (p < 0.05) by up-regulating Bax, caspase-3, and caspase-9, and down-regulating Bcl-2. The expression of genes associated with inflammation-related NF-κB, iNOS, and COX-2 genes, was significantly down-regulated, and IκB-α was up-regulated (p < 0.05). These results suggest that PLCSB is a potent preventive against in vivo colon carcinogenesis and that PLCSB with an RS3 carrier could increase the preventative effect in mice.     

Novel Pyrimidine Derivatives as Potential Anticancer Agents: Synthesis,Biological Evaluation and Molecular Docking Study

In the present paper, new pyrimidine derivatives were designed, synthesized and analyzed in terms of their anticancer properties. The tested compounds were evaluated in vitro for their antitumor activity. The cytotoxic effect on normal human dermal fibroblasts (NHDF) was also determined. According to the results, all the tested compounds exhibited inhibitory activity on the proliferation of all lines of cancer cells (colon adenocarcinoma (LoVo), resistant colon adenocarcinoma (LoVo/DX), breast cancer (MCF-7), lung cancer (A549), cervical cancer (HeLa), human leukemic lymphoblasts (CCRF-CEM) and human monocytic (THP-1)). In particular, their feature stronger influence on the activity of P-glycoprotein of cell cultures resistant to doxorubicin than doxorubicin. Tested compounds have more lipophilic character than doxorubicin, which determines their affinity for the molecular target and passive transport through biological membranes. Moreover, the inhibitory potential against topoisomerase II and DNA intercalating properties of synthesized compounds were analyzed via molecular docking.     

Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4-Ethylenedioxythiophenyl-2-propen-1-one Analogues

A new series of 3,4-ethylenedioxythiophene (EDOT)-appended propenones were prepared by condensation reaction and their in vitro cytotoxicity effects were evaluated against five human cancer cell lines. Preliminary structure–activity relationships of EDOT-incorporated 2-propenone derivatives were also established. The EDOT-appended enones demonstrated significant cytotoxicity against human cancer cell lines. The most active analogue, (E)-3-(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one ( 3 p , GI₅₀=110 nm ), severely inhibited the clonogenic potential of cancer cells, and induced cell-cycle arrest in the G2/M phase and caused an accumulation of HCT116 colon cancer cells with >4 N DNA content. Also, 3 p exhibited weak inhibition of the enzymatic activity of human topoisomerase I. Molecular docking studies indicated preferential binding of the compounds to the ATP-binding pocket of the human checkpoint 2 kinase (Chk2) catalytic domain, thus, identifying a novel diaryl 2-propenone chemotype for the development of potent inhibitors of Chk2.     

Discovery of a Nanomolar Multikinase Inhibitor (KST016366): A New Benzothiazole Derivative with Remarkable Broad‐Spectrum Antiproliferative Activity

Herein we report the discovery of compound 6 [KST016366; 4‐((2‐(3‐(4‐((4‐ethylpiperazin‐1‐yl)methyl)‐3‐(trifluoromethyl)phenyl)ureido)benzo[d]thiazol‐6‐yl)oxy)picolinamide] as a new potent multikinase inhibitor through minor structural modification of our previously reported RAF kinase inhibitor A . In vitro anticancer evaluation of 6 showed substantial broad‐spectrum antiproliferative activity against 60 human cancer cell lines. In particular, it showed GI₅₀ values of 51.4 and 19 nm against leukemia K‐562 and colon carcinoma KM12 cell lines, respectively. Kinase screening of compound 6 revealed its nanomolar‐level inhibitory activity of certain oncogenic kinases implicated in both tumorigenesis and angiogenesis. Interestingly, 6 displays IC₅₀ values of 0.82, 3.81, and 53 nm toward Tie2, TrkA, and ABL‐1 (wild‐type and T315I mutant) kinases, respectively. Moreover, 6 is orally bioavailable with a favorable in vivo pharmacokinetic profile. Compound 6 may serve as a promising candidate for further development of potent anticancer chemotherapeutics.     

Glycogen Synthase Kinase 3β Inhibition as a Therapeutic Approach in the Treatment of Endometrial Cancer

Alternative strategies beyond current chemotherapy and radiation therapy regimens are needed in the treatment of advanced stage and recurrent endometrial cancers. There is considerable promise for biologic agents targeting the extracellular signal-regulated kinase (ERK) pathway for treatment of these cancers. Many downstream substrates of the ERK signaling pathway, such as glycogen synthase kinase 3β (GSK3β), and their roles in endometrial carcinogenesis have not yet been investigated. In this study, we tested the importance of GSK3β inhibition in endometrial cancer cell lines and in vivo models. Inhibition of GSK3β by either lithium chloride (LiCl) or specific GSK3β inhibitor VIII showed cytostatic and cytotoxic effects on multiple endometrial cancer cell lines, with little effect on the immortalized normal endometrial cell line. Flow cytometry and immunofluorescence revealed a G2/M cell cycle arrest in both type I (AN3CA, KLE, and RL952) and type II (ARK1) endometrial cancer cell lines. In addition, LiCl pre-treatment sensitized AN3CA cells to the chemotherapy agent paclitaxel. Administration of LiCl to AN3CA tumor-bearing mice resulted in partial or complete regression of some tumors. Thus, GSK3β activity is associated with endometrial cancer tumorigenesis and its pharmacologic inhibition reduces cell proliferation and tumor growth.     

Promising Anticancer Activity of [Bis(1,8-quinolato)palladium (II)] Alone and in Combination

Due to similar coordination chemistry of palladium and platinum, a large number of palladium compounds as well have been investigated for their anticancer activity. In the present study, we describe synthesis, characterization, and anticancer activity of palladium complex [Bis(1,8-quinolato)palladium (II)], coded as NH3 against seven different cancer cell lines. NH3 is found to have higher antitumor activity than cisplatin against both parent ovarian A2780 cell line and cisplatin-resistant cell lines. Also, NH3 has the lower IC₅₀ value in HT-29 colorectal cancer cell line. The higher antitumor activity of NH3 is due to the presence of bulky 8-Hydroxyquinoline ligand, thus reducing its reactivity. Proteomic study has identified significantly expressed proteins which have been validated through bioinformatics. NH3 has been found to be less toxic than cisplatin at 2.5 mg/kg and 5 mg/kg dosages on mice models. Binary combinations of NH3 with curcumin and epigallocatechin gallate (EGCG) have demonstrated dose and sequence-dependent synergism in ovarian and colorectal cancer models. All of the preclinical studies indicate promising therapeutic potential of NH3 [Bis(1,8-quinolato)palladium (II)] as an anticancer drug.     

Cancer Cell Cytotoxicities of 1-(4-Substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine Derivatives

A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a-g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and (1)H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B), breast (MCF7, BT20, T47D, CAMA-1), colon (HCT-116), gastric (KATO-3) and endometrial (MFE-296) cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compound. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines.     

Influence of Ce3+ Substitution on Antimicrobial and Antibiofilm Properties of ZnCexFe2−xO4 Nanoparticles (X = 0.0, 0.02, 0.04, 0.06, and 0.08) Conjugated with Ebselen and Its Role Subsidised with γ-Radiation in Mitigating Human TNBC and Colorectal Adenocarcinoma Proliferation In Vitro

Cancers are a major challenge to health worldwide. Spinel ferrites have attracted attention due to their broad theranostic applications. This study aimed at investigating the antimicrobial, antibiofilm, and anticancer activities of ebselen (Eb) and cerium-nanoparticles (Ce-NPs) in the form of ZnCe_xFe_2−XO₄ on human breast and colon cancer cell lines. Bioassays of the cytotoxic concentrations of Eb and ZnCe_xFe_2−XO₄, oxidative stress and inflammatory milieu, autophagy, apoptosis, related signalling effectors, the distribution of cells through the cell-cycle phases, and the percentage of cells with apoptosis were evaluated in cancer cell lines. Additionally, the antimicrobial and antibiofilm potential have been investigated against different pathogenic microbes. The ZOI, and MIC results indicated that ZnCe_xFe_2−XO₄; X = 0.06 specimen reduced the activity of a wide range of bacteria and unicellular fungi at low concentration including P. aeruginosa (9.5 mm; 6.250 µg/mL), S. aureus (13.2 mm; 0.390 µg/mL), and Candida albicans (13.5 mm; 0.195 µg/mL). Reaction mechanism determination indicated that after ZnCe_xFe_2−xO₄; X = 0.06 treatment, morphological differences in S. aureus were apparent with complete lysis of bacterial cells, a concomitant decrease in the viable number, and the growth of biofilm was inhibited. The combination of Eb with ZFO or ZnCe_xFe_2−XO₄ with γ-radiation exposure showed marked anti-proliferative efficacy in both cell lines, through modulating the oxidant/antioxidant machinery imbalance, restoring the fine-tuning of redox status, and promoting an anti-inflammatory milieu to prevent cancer progression, which may be a valuable therapeutic approach to cancer therapy and as a promising antimicrobial agent to reduce the pathogenic potential of the invading microbes.