Growth Inhibition Of HeLa Cells Research Articles

Synergistic cytotoxicity and in vitro antioxidant activity of hederagenin and its glycoside from quinoa.

Although a series of studies confirm the bioactivities of hederagenin and its glycosides, their synergistic effects and potential mechanisms are still worthy of further exploration. This work investigated the synergistic cytotoxicity and in vitro antioxidant activity of hederagenin and hederagenin 28-O-β-d-glucopyranoside (28-Glc-hederagenin). Hederagenin and 28-Glc-hederagenin inhibited HeLa cell growth and their combination further strengthened this effect. The combination of hederagenin and 28-Glc-hederagenin significantly increased the rate of apoptotic cells, suggesting the presence of a synergistic effect between the two substances. This combination also enhanced in vitro antioxidant activity compared with individual treatments. A network pharmacology and molecular docking-based approach was performed to explore the underlying mechanisms of hederagenin and 28-Glc-hederagenin against cervical cancer and oxidant damage. This work identified 18 related Kyoto Encyclopedia of Genes and Genome pathways, 202 related biological process terms, 17 related CC terms, and 35 related molecular function terms and then revealed 30 nodes and 196 edges. Subsequently, two highly connected clusters and the top four targets were identified. Molecular docking showed potent binding affinity of hederagenin and 28-Glc-hederagenin toward core targets associated with both cervical cancer and oxidant damage. This work may provide scientific basis for the combined use of hederagenin and its glycosides as dietary supplements.

Ellagic Acid from Hull Blackberries: Extraction, Purification, and Potential Anticancer Activity.

Ellagic acid (EA) is present at relatively high concentrations in many berries and has many beneficial health effects, including anticancer properties. To improve the development and utilization of blackberry fruit nutrients, we divided Hull blackberry fruits into five growth periods according to color and determined the EA content in the fruits in each period. The EA content in the green fruit stage was the highest at 5.67 mg/g FW. Single-factor tests and response surface methodology were used to optimize the extraction process, while macroporous resin adsorption and alkali dissolution, acid precipitation, and solvent recrystallization were used for purification. The highest purity of the final EA powder was 90%. The anticancer assessment results determined by MTT assay showed that EA inhibited HeLa cells with an IC50 of 35 μg/mL, and the apoptosis rate of the cells increased in a dose-dependent manner, with the highest rate of about 67%. We evaluated the changes in the mRNA levels of genes related to the EA-mediated inhibition of cancer cell growth and initially verified the PI3K/PTEN/AKT/mTOR pathway as the pathway by which EA inhibits HeLa cell growth. We hope to provide a theoretical basis for the deep exploration and utilization of this functional food.

Structural and Thermomagnetic Properties of Gallium Nanoferrites and Their Influence on Cells In Vitro.

Magnetite and gallium substituted cuboferrites with a composition of GaxFe3-xO4 (0 ≤ x ≤ 1.4) were fabricated by thermal decomposition from acetylacetonate salts. The effect of Ga3+ cation substitution on the structural and thermomagnetic behavior of 4-12 nm sized core-shell particles was explored by X-ray and neutron diffraction, small angle neutron scattering, transmission electron microscopy, Mössbauer spectroscopy, and calorimetric measurements. Superparamagnetic (SPM) behavior and thermal capacity against increasing gallium concentration in nanoferrites were revealed. The highest heat capacity typical for Fe3O4@Ga0.6Fe2.4O4 and Ga0.6Fe2.4O4@Fe3O4 is accompanied by a slight stimulation of fibroblast culture growth and inhibition of HeLa cell growth. The observed effect is concentration dependent in the range of 0.01-0.1 mg/mL and particles of Ga0.6Fe2.4O4@Fe3O4 design have a greater effect on cells. Observed magnetic heat properties, as well as interactions with tumor and healthy cells, provide a basis for further biomedical research to use the proposed nanoparticle systems in cancer thermotherapy (magnetic hyperthermia).

Cytotoxic activity of Galantamine hydrobromide against HeLa cell line

Cytotoxic activity of Galantamine HBr against human cervical adenocarcinoma cell line HeLa in different concentrations (1.875 μМ ÷ 30 μМ) was evaluated. Inhibition of HeLa cell growth after treatment with Galantamine HBr and index of cell viability were determined. From the experimental results was proven that the drug exerts cytotoxic activity towards HeLa cell line, with antiproliferative activity presented as the value of IC50 = 30 μM ± 0.22.

Cytotoxicity, Apoptosis Induction, Oxidative Stress, and Cell Cycle Arrest of Clerodendrum chinense Flower Extract Nanoparticles in HeLa Cells

Clerodendrum chinense is a plant containing numerous secondary active metabolites. This study aimed to evaluate the antioxidant and anti-cancer activities of C. chinense flower ethanolic extract and identify the bioactive compounds. High-performance liquid chromatography was used to identify and quantify the bioactive compounds of the extract. The antioxidant activity of the extract was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) free radical scavenging assays and the Ferric Reducing Antioxidant Power Assay (FRAP). The cytotoxicity of C. chinense flower ethanolic extract against A549, MCF-7 and HeLa cells was determined using the sulforhodamine B (SRB) assay. Nanoparticles (NPs) of C. chinense flower extract were fabricated using a solvent displacement method. Then the anti-cancer activities of the extract and NPs were confirmed by cytotoxicity, cell apoptotic induction, reactive oxygen species (ROS) formation, colony formation and cell cycle assays against HeLa cervical cancer cells. C. chinense flower extract and NPs showed significant free radical scavenging activities and ferric-reducing power. As shown by Pearson’s correlation coefficients, the total phenolic and total flavonoid contents of C. chinense flower extract and NPs significantly correlated with antioxidant activity. C. chinense flower extract demonstrated antiproliferative activity against A549, MCF-7 and HeLa cancer cells after treatment for 24, 48 and 72 h. The growth inhibition of HeLa cells mediated by C. chinense flower extract and NPs appears to be associated with apoptosis, ROS formation and cell cycle arrest. Thus, this study provided evidence of the anticervical cancer potentials of C. chinense flower ethanolic extract and NPs. Keywords: Natural products, Nanoparticles, Pharmaceutical, Phenolic compounds, Plant extract, Clerodendrum chinense

Natural Gallic Acid and Methyl Gallate Induces Apoptosis in Hela Cells through Regulation of Intrinsic and Extrinsic Protein Expression.

Induction of apoptosis is one of the targeted approaches in cancer therapies. As previously reported, natural products can induce apoptosis in in vitro cancer treatments. However, the underlying mechanisms of cancer cell death are poorly understood. The present study aimed to elucidate cell death mechanisms of gallic acid (GA) and methyl gallate (MG) from Quercus infectoria toward human cervical cancer cell lines (HeLa). The antiproliferative activity of GA and MG was characterised by an inhibitory concentration using 50% cell populations (IC50) by an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Cervical cancer cells, HeLa, were treated with GA and MG for 72 h and calculated for IC50 values. The IC50 concentration of both compounds was used to elucidate the apoptotic mechanism using acridine orange/propidium iodide (AO/PI) staining, cell cycle analysis, the Annexin-V FITC dual staining assay, apoptotic proteins expressions (p53, Bax and Bcl-2) and caspase activation analysis. GA and MG inhibited the growth of HeLa cells with an IC50 value of 10.00 ± 0.67 µg/mL and 11.00 ± 0.58 µg/mL, respectively. AO/PI staining revealed incremental apoptotic cells. Cell cycle analysis revealed an accumulation of cells at the sub-G1 phase. The Annexin-V FITC assay showed that cell populations shifted from the viable to apoptotic quadrant. Moreover, p53 and Bax were upregulated, whereas Bcl-2 was markedly downregulated. Activation of caspase 8 and 9 showed an ultimate apoptotic event in HeLa cells treated with GA and MG. In conclusion, GA and MG significantly inhibited HeLa cell growth through apoptosis induction by the activation of the cell death mechanism via extrinsic and extrinsic pathways.

A co-delivery system based on chlorin e6-loaded ROS-sensitive polymeric prodrug with self-amplified drug release to enhance the efficacy of combination therapy for breast tumor cells.

Background: Recently, various combination therapies for tumors have garnered popularity because of their synergistic effects in improving therapeutic efficacy and reducing side effects. However, incomplete intracellular drug release and a single method of combining drugs are inadequate to achieve the desired therapeutic effect. Methods: A reactive oxygen species (ROS)-sensitive co-delivery micelle (Ce6@PTP/DP). It was a photosensitizer and a ROS-sensitive paclitaxel (PTX) prodrug for synergistic chemo-photodynamic therapy. Micelles size and surface potential were measured. In vitro drug release, cytotoxicity and apoptosis were investigated. Results: Ce6@PTP/DP prodrug micelles exhibited good colloidal stability and biocompatibility, high PTX and Ce6 loading contents of 21.7% and 7.38%, respectively. Upon light irradiation, Ce6@PTP/DP micelles endocytosed by tumor cells can generate sufficient ROS, not only leading to photodynamic therapy and the inhibition of tumor cell proliferation, but also triggering locoregional PTX release by cleaving the thioketal (TK) bridged bond between PTX and methoxyl poly (ethylene glycol). Furthermore, compared with single drug-loaded micelles, the light-triggered Ce6@PTP/DP micelles exhibited self-amplified drug release and significantly greater inhibition of HeLa cell growth. Conclusion: The results support that PTX and Ce6 in Ce6@PTP/DP micelles exhibited synergistic effects on cell-growth inhibition. Thus, Ce6@PTP/DP micelles represent an alternative for realizing synergistic chemo-photodynamic therapy.

Novel Peptide from the Hydrolysate of Hybrid Sturgeon (Acipenseridae) Spinal Cord: Isolation, Identification, and Anti-proliferative Effects in Human Cervix Cancer Cells.

Anti-proliferative peptides have recently attracted attention for their excellent bioactivity and biocompatibility. In this paper, five novel anti-proliferative peptides were identified from the hydrolysate of hybrid sturgeon spinal cord (HSSC). In addition, the structure-activity relationship of the novel anti-proliferative peptides was explored. In vitro experiments indicated that the peptide "VDSVLDVVRK" presented the highest inhibition of HeLa cell growth in all samples (IC50 = 2.5 μM). VDSVLDVVRK showed a random coil secondary structure and nanomicelles in the tumor microenvironment. Transmission electron microscopy results confirmed that nanomicelles disassemble as the concentration of VDSVLDVVRK decreases. Furthermore, VDSVLDVVRK could induce HeLa cell apoptosis by increasing the expression of Cyt-c (98.65 ± 1.85%, p < 0.01) and caspase-9 (39.85 ± 1.81%, p < 0.01). In this study, the anti-proliferative mechanism of the HSSC peptide was discussed, which provided a theoretical basis for the research and development of anti-proliferative functional food.

Aza-SAHA Derivatives Are Selective Histone Deacetylase 10 Chemical Probes That Inhibit Polyamine Deacetylation and Phenocopy HDAC10 Knockout.

We report the first well-characterized selective chemical probe for histone deacetylase 10 (HDAC10) with unprecedented selectivity over other HDAC isozymes. HDAC10 deacetylates polyamines and has a distinct substrate specificity, making it unique among the 11 zinc-dependent HDAC hydrolases. Taking inspiration from HDAC10 polyamine substrates, we systematically inserted an amino group ("aza-scan") into the hexyl linker moiety of the approved drug Vorinostat (SAHA). This one-atom replacement (C→N) transformed SAHA from an unselective pan-HDAC inhibitor into a specific HDAC10 inhibitor. Optimization of the aza-SAHA structure yielded the HDAC10 chemical probe DKFZ-748, with potency and selectivity demonstrated by cellular and biochemical target engagement, as well as thermal shift assays. Cocrystal structures of our aza-SAHA derivatives with HDAC10 provide a structural rationale for potency, and chemoproteomic profiling confirmed exquisite cellular HDAC10-selectivity of DKFZ-748 across the target landscape of HDAC drugs. Treatment of cells with DKFZ-748, followed by quantification of selected polyamines, validated for the first time the suspected cellular function of HDAC10 as a polyamine deacetylase. Finally, in a polyamine-limiting in vitro tumor model, DKFZ-748 showed dose-dependent growth inhibition of HeLa cells. We expect DKFZ-748 and related probes to enable further studies on the enigmatic biology of HDAC10 and acetylated polyamines in both physiological and pathological settings.

Fabrication of cell penetrating peptide labelled biodegradable poly(methacrylamide) nanoparticles for delivery of doxorubicin in HeLa cells

Advancements in cancer nano-therapeutics have led to the development of new and improved drug delivery systems but challenges still persist in the form of several limitations such as ineffective drug distribution, poor water solubility, and drug degradation. In lieu of this, the aim of this work is the development of a highly efficient nanomaterial based drug delivery system to overcome these limitations. In this work, we have successfully developed a theranostic platform where biodegradable polymeric nanoparticles have been used to reduce drug toxicity, control drug release, and provide biocompatibility with enhanced bioimaging. Anticancer drug, doxorubicin (DOX) was encapsulated in polymeric nanoparticles composed of P(N-(3-aminopropyl) methacrylamide) homopolymer, P(APMA), bearing primary amines for further modification. Water soluble CdTe quantum dots (QDs) were used as the fluorescent tag. The encapsulation efficiency of QDs-DOX conjugates into polymeric nanoparticles was found to be very high. To enhance the cellular internalization, a cell penetrating peptide BP100 (KKLFKKILKYL-Amide) was also attached on the surface of these polymeric nanoparticles and characterized using confocal microscopy. The drug release from the nanoconjugates at acidic pH showed enhanced internalization and growth inhibition in HeLa cells. Therefore, the synthesized conjugates can act as promising candidate for the successful treatment of cancer.

Resveratrol inhibits HeLa cell proliferation by regulating mitochondrial function

The beneficial roles of resveratrol (RES) in affecting proliferation of multiple cancer cells have attracted intensive attention. However, the underlying mechanism remains unclear. This study aims to bridge the knowledge gap by investigating RES-induced growth inhibition of HeLa cells. Our work focuses on the metergasis of mitochondria in the RES-exposed cells. Therefore, HeLa cells were treated with different concentrations of RES for 30 min and 24 h, respectively. As a result, concentration-dependent increases in cell growth inhibition, ROS (reactive oxygen species) triggering, and LC3-II (light chain 3-II) expression were detected in the HeLa cells exposed to RES for 24 h. Interestingly, a specific concentration-dependent effect was observed in the HeLa cells exposed to RES for 30 min, that is, low concentration RES (≤ 25 μmol/L) reduced ROS levels, inhibited transcription and expression levels of LC3-II, and stimulated mitochondrial respiratory capacities. In contrast, high concentration RES (50 and 100 μmol/L) induced ROS over-production and autophagy in the cells, resulting in decreased levels of mitochondrial membrane potential, mitochondrial DNA copy numbers, and mitochondrial respiratory capacities. Together, our data concluded that RES inhibited HeLa cell proliferation through perturbation of mitochondrial structure and function, and ROS-induced autophagy also played a critical role in the process.

Synthesis and Biological Evaluation of Highly Active 7-Anilino Triazolopyrimidines as Potent Antimicrotubule Agents.

Two different series of fifty-two compounds, based on 3′,4′,5′-trimethoxyaniline (7a–ad) and variably substituted anilines (8a–v) at the 7-position of the 2-substituted-[1,2,4]triazolo [1,5-a]pyrimidine nucleus, had moderate to potent antiproliferative activity against A549, MDA-MB-231, HeLa, HT-29 and Jurkat cancer cell lines. All derivatives with a common 3-phenylpropylamino moiety at the 2-position of the triazolopyrimidine scaffold and different halogen-substituted anilines at its 7-position, corresponding to 4′-fluoroaniline (8q), 4′-fluoro-3′-chloroaniline (8r), 4′-chloroaniline (8s) and 4′-bromoaniline (8u), displayed the greatest antiproliferative activity with mean IC50′s of 83, 101, 91 and 83 nM, respectively. These four compounds inhibited tubulin polymerization about 2-fold more potently than combretastatin A-4 (CA-4), and their activities as inhibitors of [3H]colchicine binding to tubulin were similar to that of CA-4. These data underlined that the 3′,4′,5′-trimethoxyanilino moiety at the 7-position of the [1,2,4]triazolo [1,5-a]pyrimidine system, which characterized compounds 7a–ad, was not essential for maintaining potent antiproliferative and antitubulin activities. Compounds 8q and 8r had high selectivity against cancer cells, and their interaction with tubulin led to the accumulation of HeLa cells in the G2/M phase of the cell cycle and to apoptotic cell death through the mitochondrial pathway. Finally, compound 8q significantly inhibited HeLa cell growth in zebrafish embryos.

P2X7 receptor involved in antitumor activity of atractylenolide I in human cervical cancer cells

Atractylenolide I (Atr-I) was found to sensitize a variety of human cancer cells in previous studies. Purinergic P2X7R plays important role in different cancers. However, whether Atr-I could generate antitumor activity in human cervical cancer cells and P2X7R get involved in this effect remain unclear. In this study, Hela (HPV 18 +) and SiHa (HPV 16 +) cells were treated with different doses of Atr-I. The results indicated that agonist and antagonist of P2X7 receptors, BzATP and JNJ-47965567 (JNJ), could suppress the proliferation of Hela and SiHa cells. Atr-I demonstrated a considerable antitumor effect in both human cervical cancer cells in vitro. Atr-I combined with P2X7R agonist, BzATP, restored Atr-I-induced growth inhibition in Hela cells but not in SiHa cells. However, the combinatorial treatment of P2X7R antagonist JNJ and Atr-I has an additive effect on cell growth inhibition in SiHa cells rather than in Hela cells. It implied that P2X7R would get involved in the anti-human cervical cancer cells effect of Atr-I.

Cytotoxic mechanism of tioconazole involves cell cycle arrest at mitosis through inhibition of microtubule assembly.

The online version contains supplementary material available at 10.1007/s10616-021-00516-w.

A metal‐organic framework ZJU‐136‐Ce for combined chemotherapy and chemodynamic therapy

AbstractA metal‐organic framework ZJU‐136‐Ce with ideal water stability was synthesized. It was adopted to load Mn2+ and DOX for chemo/chemodynamic therapy of tumor, the loading capacity of Mn2+ and DOX was 0.87 wt % and 10.19 wt % in ZJU‐136‐Ce, respectively. DOX&amp;Mn@ZJU‐136‐Ce exhibited significant effects of inhibition of Hela cell growth, which confirmed it had a potential application prospect in the multimodal cancer therapy.

Synthesis, characterization, anticancer activity assessment and apoptosis signaling of fucoidan mediated copper oxide nanoparticles

Nanotechnology is expanding at a very fast rate owing to its many possible applications in the industrial, biomedical, commercial, and other areas. In this study, copper oxide nanoparticles (CuO-Fu-NPs) were prepared using Undaria pinnatifida -derived fucoidan as a capping and reducing agent, and their anticancer activity and apoptosis-related mechanism were assessed using HeLa cells. Fourier-transform infrared spectroscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, and X-ray powder diffraction were used to characterize the fabricated product, revealing that the fucoidan molecules had reduced the Cu ions into NPs and coated the CuO NP surface. Circular NPs of <30 nm in size were also trapped in fucoidan sheets. The CuO-Fu-NPs inhibited HeLa cell growth significantly in a dose- and time-dependent manner, with an IC 50 value of 0.479 mg/mL (compared with 1.104 mg/mL with fucoidan alone). According to TUNEL assay results, the CuO-Fu-NPs induced DNA damage and apoptosis in the HeLa cells. Western blot analysis revealed the expression of apoptosis-associated proteins (BCL2, BAX, cytochrome c , cleaved CASP-3 (cleaved caspase-3), and cleaved PARP) in the CuO-Fu-NPs-treated cells. This study provides valuable information about the toxic effect of this biomaterial, which could have biomedical applications.

Potential anticancer activity of Acetone extracts of Toona cilliata, Seriphium plumosum and Schkuhria pinnata on HeLa cervical cancer cells.

Cervical cancer is common in women in less developed regions of the world. The plant biomolecules can be employed for synergistic activity with chemo- and radiotherapy. This combinations might result in reduced toxicity and increased efficacy of the treatment regimen. The anti-HeLa cells activity of the acetone extracts of S. plumosum, T. cilliata and S. pinnata was assessed using different parameters. Secondary metabolite detection and antioxidant activity quantification were determined using the DPPH and ferric iron reducing assays. HeLa cell growth inhibition and mechanistics were assessed by employing MTT and Annexin-V flous assays. Observations revealed the presence of phenolic, flavonoids, tannins steroids and coumarins in all the plants extracts. High amount of total phenolic and flavonoid content were detected in S. plumosum and T. cilliata. S. plumosum extract had the best DPPH scavenging activity and ferric reducing powers. Observable concentration dependent cell proliferation inhibition by test materials was exhibited. The leaf extracts from T. cilliata, S. plumosum and S. pinnata contain compounds of various polarities with free-radical, antioxidant and anti-cancerous activities that may play a beneficial role in treatment.

Digitoxin inhibits HeLa cell growth through the induction of G2/M cell cycle arrest and apoptosis in vitro and in vivo.

Cervical cancer is the fourth most common gynecological malignancy affecting the health of women worldwide and the second most common cause of cancer‑related mortality among women in developing regions. Thus, the development of effective chemotherapeutic drugs for the treatment of cervical cancer has become an important issue in the medical field. The application of natural products for the prevention and treatment of various diseases, particularly cancer, has always attracted widespread attention. In the present study, a library of natural products composed of 78single compounds was screened and it was found that digitoxin exhibited the highest cytotoxicity against HeLa cervical cancer cells with an IC50 value of 28nM at 48h. Furthermore, digitoxin exhibited extensive antitumor activities in a variety of malignant cell lines, including the lung cancer cell line, A549, the hepatoma cell line, MHCC97H, and the colon cancer cell line, HCT116. Mechanistically, digitoxin caused DNA double‑stranded breaks (DSBs), inhibited the cell cycle at the G2/M phase via the ataxia telangiectasia mutated serine/threonine kinase (ATM)/ATM and Rad3‑related serine/threonine kinase (ATR)‑checkpoint kinase (CHK1)/checkpoint kinase 2 (CHK2)‑Cdc25C pathway and ultimately triggered mitochondrial apoptosis, which was characterized by the disruption of Bax/Bcl‑2, the release of cytochrome c and the sequential activation of caspases and poly(ADP‑ribose) polymerase(PARP). In addition, the invivo anticancer effect of digitoxin was confirmed in HeLa cell xenotransplantation models. On the whole, the findings of the present study demonstrate the efficacy of digitoxin against cervical cancer invivo and elucidate its molecular mechanisms, including DSBs, cell cycle arrest and mitochondrial apoptosis. These results will contribute to the development of digitoxin as a chemotherapeutic agent in the treatment of cervical cancer.

Silibinin Induces G2/M Cell Cycle Arrest by Activating Drp1-Dependent Mitochondrial Fission in Cervical Cancer.

Cervical cancer is the fourth leading cancer type and the second most common gynecological malignancy among women worldwide. Silibinin (SB), a chief bioactive natural polyphenolic flavonoid of Silybum marianum L., has been used clinically for its hepatocyte protective effects. It also has anticancer effects via the induction of apoptosis and cell cycle arrest. However, the effects of SB on cervical cancer cells through mitochondrial fission have not been studied. Here, we showed that SB markedly suppressed cervical cell proliferation by inducing G2/M cell cycle arrest via the activation of dynamin-related protein 1 (Drp1), which in turn mediated the mitochondrial fission dysfunction both in vitro and in vivo. SB decreased the ATP content, mitochondrial membrane potential, and mtDNA copy number, as well as reduced the reactive oxygen species levels in cervical cells. Furthermore, SB induced excessive mitochondrial fragmentation and reduced tubule formation. Further study showed that knockdown of Drp1 abolished the SB-induced G2/M cell cycle arrest in cervical cancer cells by inhibiting the mitochondrial fission pathway. More importantly, SB inhibited Hela cell growth in vivo model. In conclusion, we are the first to demonstrate that SB induces cervical cancer cell G2/M cell cycle arrest by activating Drp1-dependent mitochondrial fission dysfunction. This study suggests the strategy of inducing Drp1-dependent mitochondrial fission for cervical cancer prevention and treatment.

Anti-proliferative Effects of Chromones: Potent Derivatives Affecting Cell Growth and Apoptosis in Breast, Bone-marrow and Cervical Cancer Cells

Previously, we have identified 3,3'-carbonyl-bis(chromones) (1a-h, 5e) and 3-(5-(benzylideneamino)thiozol-3-yl)-2H-chromen-2-ones (7a-j) as potent inhibitors of tissue non-specific alkaline phosphatase (TNAP). The present study was designed to investigate the cytotoxic and pro-apoptotic effect of the said derivatives. The anti-proliferative effect of the derivatives was investigated in three cancer cell lines i.e., MCF-7, K-562, HeLa and normal BHK21 cells using MTT assay. The pro-apoptotic effect of the most potent derivatives was investigated by using flow cytometry, DAPI and PI staining and DNA binding studies. Among all the screened compounds, 1f, 1d, 1c (from 3,3'-carbonyl-bis(chromones), 7c, 7h and 7i (from 3-(5-(benzylideneamino)thiozol-3-yl)-2H-chromen-2-ones) exhibited remarkable growth inhibitory effects. Compounds 1f and 7c were found to be the most potent cytotoxic derivatives against MCF-7; 1d and 7h inhibited most of the proliferation of K-562 cells, whereas 1c and 7i showed maximum growth inhibition in HeLa cells. The identified compounds exerted lower micromolar potency against the respective cell line with significant selectivity over the normal cells (BHK-21). The identified compounds also induced either G2 or S-phase arrest within the respective cancer cells, chromatin condensation and nuclear fragmentation, as well as maximum interaction with DNA. These results provide evidence that the characteristic chemical features of attached groups are the key factors for their anticancer effects and play a useful role in revealing the mechanisms of action in relation to the known compounds in future research programs.