Human Cervical Cancer HeLa Cells Research Articles

Oxidative Stress Mediated Cytotoxicity, Cell Cycle Arrest, and Apoptosis Induced by Rosa damascena in Human Cervical Cancer HeLa Cells.

Rosa damascena Mill (Damask rose), belonging to the Rosaceae family, is known for medicinal purposes in traditional medicine system. However, its anticancer activity has not been studied yet in detail. Herein, we aimed to investigate the cytotoxic effects of R. damascena hexane (RA-HE) and methanolic (RA-ME) extracts against human breast (MCF-7), lung epithelial (A-549), and cervical (HeLa) cancer cells. The RA-HE and RA-ME showed more potent cytotoxic effects against HeLa cells with an IC50 of 819.6 and 198.4 μg/ml, respectively. Further, cytotoxic concentrations of most effective extract (RA-ME) were used to evaluate the mechanism of cytotoxicity involved in HeLa cells. A concentration-dependent induction of lipid peroxidation (LPO) and reduction of glutathione (GSH) in HeLa cells treated with 250-1000 μg/ml of RA-ME confirms the association of oxidative stress. We also detected a noteworthy increase in reactive oxygen species (ROS) production and a decline in mitochondrial membrane potential (MMP) level in RA-ME-exposed HeLa cells. Flow cytometric data showed a strong dose-response relationship in cell cycle analysis between subG1 phase in HeLa cells and RA-ME treatment. Similarly, a concentration-dependent increase was recorded with Annexin V assay in HeLa cells going to late apoptosis. In conclusion, our findings suggest that RA-ME-induced cytotoxicity and apoptosis in HeLa cells are mediated by oxidative stress.

Metformin and arsenic trioxide synergize to trigger Parkin/pink1-dependent mitophagic cell death in human cervical cancer HeLa cells.

Mitochondria are involved in various biological processes including intracellular homeostasis, proliferation, senescence, and death, and mitochondrial mitophagy is closely related to the development and regression of malignant tumors. Recent studies confirmed that the hypoglycemic drug metformin (Met) exerted various antitumor effects, protected neural cells, and improved immunity, while arsenic trioxide (ATO) is an effective chemotherapeutic agent for the clinical treatment of leukemia and various solid tumors. However, the possible combined antitumor effects of Met and ATO and their cellular molecular mechanisms are unclear. We investigated the role of Parkin-mediated mitochondrial mitophagy in the anti-tumor mechanism of Met and ATO by studying the effects of Met and/or ATO on the proliferation and apoptosis of cervical cancer HeLa cells. Both Met and ATO effectively inhibited the proliferative activity of HeLa cells and induced apoptosis by activating Bax and inhibiting Bcl-2. Met and ATO treatment alone or in combination stimulated mitophagosome accumulation in HeLa cells, increased the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II, and decreased levels of the mitophagic lysosomal substrate protein P62. The mitochondrial membrane potential of HeLa cells also decreased, accompanied by activation of the mitochondrial translocase TOM system and the Pink1/Parkin signaling pathway. These results suggested that Met and/or ATO could induce mitophagy in HeLa cells via the Pink1/Parkin signaling pathway, leading to mitophagic apoptosis and inhibition of tumor cell proliferation. The combination of Met and ATO thus has enhanced antitumor effects, suggesting that this combination has potential clinical applications for the treatment of cervical cancer and other tumors.

Ginsenoside CK induces apoptosis of human cervical cancer HeLa cells by regulating autophagy and endoplasmic reticulum stress.

Ginsenoside CK (GCK), as a metabolite of ginsenoside Rb1, has been studied for its anti-cancer activity. However, its in-depth anti-cancer mechanism on cervical cancer (CC) HeLa cells has not been fully elucidated. This study found that GCK inhibited the proliferation of CC HeLa cells and caused alteration in cell morphology with an IC50 of 45.95 μM. At the same time, GCK treatment blocked the cell cycle in the G0/G1 phase, elevated the reactive oxygen species (ROS) level, decreased mitochondrial membrane potential (Δψm), contributed to Ca2+ leakage, inhibited HeLa cell metastasis, and stimulated the key markers related to apoptosis, mitochondrial and endoplasmic reticulum pathways. GCK altered the regulation of the Caspase family, Bak/Bcl-xl and down-regulated the endoplasmic reticulum pathways (PERK and IRE1α). Starting from flow cytometry and the protein level, we found that autophagy inhibitors inhibited autophagy while promoting apoptosis, and apoptosis inhibitors reduced the rate of apoptosis while promoting autophagy, which proved that GCK can be used as a suitable novel natural product for CC treatment.

Bersaldegenin-1,3,5-orthoacetate induces caspase-independent cell death, DNA damage and cell cycle arrest in human cervical cancer HeLa cells

Context Bufadienolide compounds occur in many plants and animal species and have strong cardiac and anti-inflammatory properties. The compounds have been recently investigated for cytotoxic and antitumor activity. Objective The cytotoxic effect of bersaldegenin-1,3,5-orthoacetate – a bufadienolide steroid occuring in plants from Kalanchoe genus (Crassulaceae), was evaluated with cervical cancer HeLa cells in vitro. Materials and methods The cytotoxic activity of the compound (at 0.1–20.0 μg/mL) on the cells was determined by Real-Time Cell Analysis (RTCA) system for 24 h. The estimation of cell cycle arrest, reactive oxygen species (ROS) production, reduction of mitochondrial membrane potential (MMP), and caspases-3/7/9 activity in the HeLa cells treated with the compound was done by flow cytometry and luminometric technique. DNA damage in the cells was estimated by immunofluorescence staining and the comet assay with etoposide as a positive control. Results The compound had strong effect on the cells (IC50 = 0.55 μg/mL) by the suppression of HeLa cells proliferation in G2/M phase of cell cycle and induction of cell death through double-stranded DNA damage and reactive oxygen species overproduction. Furthermore, we did not observe an increase in the activity of caspase-3/7/9 in the treated cells as well as a decrease in cellular mitochondrial membrane potential. Gene expression analysis revealed the overexpression of NF-Kappa-B inhibitors genes (>2-fold higher than control) in the treated cells. Conclusions Bersaldegenin-1,3,5-orthoacetate induces cell cycle arrest and caspase-independent cell death through double-stranded DNA damage. These results are an important step in further studies on cell death signalling pathways induced by bufadienolides.

Screening of antibacterial and cytotoxicity of the copper (II) complexes of N-donor chelating ligand

Copper (II) complexes, namely dichloromono(1-amidino-O-ethylurea)copper (II), (1) and bis(1-amidino-O-ethylurea)copper (II) bromide, (2) were synthesized and characterized. The antibacterial screening of complexes 1 and 2 was performed along with their corresponding metal salts (CuCl2.2H2O) and (CuBr2), and ligand (dicyandiamide), against two human urinary pathogenic bacterial strains, Escherichia coli and Proteus mirabilis, by the disc diffusion method. All test compounds, except ligand have shown significant antibacterial activities on both bacterial strains. Their antibacterial effectiveness increased in a dose dependent manner, whereas their ability to inhibit the growth of both bacterial species decreased as their incubation time increased. The activity of complex 1 was found to be greater than its metal salt, while that of complex 2 was lower than the corresponding metal salt on both bacterial species. The in-vitro cytotoxic screening of complexes 1 and 2 was also assessed against human cervical adenocarcinoma cancer (HeLa) cell line using the MTT assay. Both complexes 1 and 2 have displayed cytotoxic effect in a dose-dependent manner with IC50 values of 59.64±6.68 µg/mL and 62.85±0.39 µg/mL, respectively. Overall, the highest antibacterial and cytotoxic activity of the present work is provided by complex 1.

Designing 3D-nanosubstrates mimicking biological cell growth: pitfalls of using 2D substrates in the evaluation of anticancer efficiency.

Designing nano-substrates (NS) that support three-dimensional (3D) cell growth using physico-chemical interventions mimicking the cellular microenvironment is highly challenging. Here we report NS that assist 3D cell development (3D NS) using multi-components on a glass substrate (2D GS), which mimics the ex vivo tissue microenvironment and promotes 3D cell growth superior to conventional 2D cell culturing methodologies. 3D NS were chemically fabricated by linking the combination of advanced materials imparting different physico-chemical traits, for example, multiwalled carbon nanotubes (CNT), graphene (G), bovine serum albumin (BSA), and iron oxide magnetic nanoparticles (MNP). We compared cell-substrate interactions resulting in cellular morphological changes, influence on the cell circularity index (CI), nuclear-cytoplasmic ratios (N/C), and nuclear compression or derangements using human colorectal carcinoma cells (HCT116) and cervical cancer (HeLa) cells. We observed the increase in N/C, extended on the 3D NS micro-environment as indicative of cellular adaptation and the transformation. HCT116 and HeLa cells on 2D GS showed an N/C ratio <0.3, and 3D NS cultured cells exhibited a higher N/C ratio (>0.5). The most significant increase in the ratio, relative to arrested cell spreading, was observed with G-3D NS. Furthermore, 3D NS were evaluated for the cell viability differentiations using the anticancer drug doxorubicin (Dox). The drug-treated cells on 3D NS demonstrated far-displaced N/C ratios compared to 2D GS. In conclusion, 3D NS systems implicate an 'in vitro to in vivo' relevance for the outcome in cell biology, cell proliferation and migration, and in anticancer drug efficacy evaluation.

Unravelling the anticancer potential of a square planar copper complex: toward non-platinum chemotherapy.

Coordination compounds from simple transition metals are robust substitutes for platinum-based complexes due to their remarkable anticancer properties. In a quest to find new metal complexes that could substitute or augment the platinum based chemotherapy we synthesized three transition metal complexes C1–C3 with Cu(ii), Ni(ii), and Co(ii) as the central metal ions, respectively, and evaluated them for their anticancer activity against the human keratinocyte (HaCaT) cell line and human cervical cancer (HeLa) cell lines. These complexes showed different activity profiles with the square planar copper complex C1 being the most active with IC50 values lower than those of the widely used anticancer drug cisplatin. Assessment of the morphological changes by DAPI staining and ROS generation by DCFH-DA assay exposed that the cell death occurred by caspase-3 mediated apoptosis. C1 displayed interesting interactions with Ct-DNA, evidenced by absorption spectroscopy and validated by docking studies. Together, our results suggest that binding of the ligand to the DNA-binding domain of the p53 tumor suppressor (p53DBD) protein and the induction of the apoptotic hallmark protein, caspase-3, upon treatment with the metal complex could be positively attributed to a higher level of ROS and the subsequent DNA damage (oxidation), generated by the complex C1, that could well explain the interesting anticancer activity observed for this complex.

Synthesis, anticancer activities and molecular modeling studies of some 2-aminonaphtho[2,3-d][1,3]thiazole-4,9-dione derivatives

Quinones, especially 1,4-naphthoquinones, are one of the most significant and widely distributed phytochemical groups in nature. 1,4-Naphthoquinones and their synthetic derivatives are found to possess remarkable cytotoxic activities. In this study, a series of 2-aminonaphtho[2,3-d][1,3]thiazole-4,9-dione derivatives were synthesized and their structures were verified with spectral analysis. In vitro cytotoxic activities of the synthesized compounds were evaluated by using MTT assay against MKN-45 (Human Gastric cancer), MDA-MB-231 (Human Breast cancer) and HeLa (Human Cervical cancer) cell lines. Among the synthesized compounds, 3d inhibited MDA-MB-cell proliferation with an IC50 value of 0.276 µM. Compound 3a inhibited HeLa and MKN-45 cell proliferation with IC50 values of 0.336 µM and 8.769 µM, respectively. Compound 3b inhibited HELA cell proliferation with an IC50 value of 0.269 µM. Molecular docking results suggest that the ligands may bind to the hDNA TopoIIβ binding pocket and partially exert their effects. These results propose that 2-aminonaphtho[2,3-d]thiazole-4,9-dion core has important biological effects and further explorations are worthwhile.

Proteomic analysis of the anticancer effect of various extracts of endemicThermopsisturcica in human cervical cancer cells

Background/aim Thermopsis turcica is a perennial species endemic to Turkey and different extracts of T. turcica have an antiproliferative effect on cancer cells, but there has not been any report on HeLa (human cervical cancer) cells. Materials and methodsTo get a better understanding of the molecular mechanism of anticancer activity of methanolic extracts of leaves (LE) and flowers (FE) of T. turcica , we employed 2-DE-based proteomics to explore the proteins involved in anticancer activity in HeLa cells. Results T. turcica extracts showed a potent cytotoxic effect on HeLa cells with the IC50 values of 1.75 mg/mL for LE and 3.25 mg/mL for FE. The induction of apoptosis by LE and FE was also consistent with increased expression of caspase mRNAs and DNA fragmentation. In terms of the proteomic approach, 27 differentially expressed proteins were detected and identified through MALDI-TOF/TOF mass spectrometry. These altered proteins were involved in cytoskeleton organization and movement, protein folding, proteolysis and translation, cell cycle and proliferation, signal transduction, cell redox homeostasis, and metabolism. ConclusionUp-regulation of protein disulfide isomerases and down-regulation of Rho GDP-dissociation inhibitor, heterogeneous nuclear ribonucleoproteins, and heat shock proteins may contribute to the induction of apoptosis and arresting of the cell cycle in HeLa cells.

Microwave-assisted extraction, partial purification and biological activity in vitro of polysaccharides from bladder-wrack (Fucus vesiculosus) by using deep eutectic solvents

Based on natural deep eutectic solvents (DESs), microwave-assisted green extraction was applied for production of polysaccharides from bladder-wrack (Fucus vesiculosus). In this study, nine different combinations of deep eutectic solvents were evaluated for extraction of polysaccharides from bladder-wrack, and the results showed that DES system composed of choline chloride and 1,4-butanediol with molar ratio of 1:5 possessed the optimal extraction efficiency for polysaccharides. A three-level and four-variable Box-Behnken design (BBD), a specific design of response surface methodology (RSM), was used to determine the optimum extraction conditions for the maximum yields of polysaccharides from bladder-wrack by using DESs. The maximum yields of polysaccharides attained 116.33 mg/g within DES water content of 32%, extraction time of 35 min, extraction temperature of 168 °C and solid–liquid ratio of 39 mg/mL. After partial separation and purification of the polysaccharides extracted by DESs, antioxidant activity and anticancer activity in vitro were evaluated. The results revealed that polysaccharides extracted from bladder-wrack exhibited excellent antioxidant activities in vitro including DPPH and ABTS radical-scavenging activity. For human cervical cancer HeLa cells, the polysaccharides possessed a strong inhibition effect on the growth rate. So these results indicate that deep eutectic solvent, as an environmentally-friendly solvent, can be applied to extract polysaccharides from multifarious plant materials.

Maslinic Acid Induces DNA Damage and Impairs DNA Repair in Human Cervical Cancer HeLa Cells.

Maslinic acid, a natural plant-derived triterpenoid compound, exhibits pharmacological activities, including anti-cancer. In the present study, we investigated the cytotoxic effects of maslinic acid on human cervical cancer HeLa cells in vitro and further investigated the molecular mechanism of maslinic acid-induced DNA damage and repair. Cell viability was measured by flow cytometry. DNA condensation (apoptotic cell death), DNA damage, and DNA fragmentation (DNA ladder) were assayed by DAPI staining, comet assay, and agarose gel electrophoresis, respectively. The expression of DNA damage and repair proteins was assayed by western blotting. Maslinic acid decreased total cell viability and induced DNA condensation, damage, and fragmentation in HeLa cells. Furthermore, maslinic acid elevated the levels of p-ATMSer1981, p-ATRSer428, p53, p-p53Ser151, p-H2A.XSer139, BRCA1 and PARP at 30-40 μM. However, it decreased the levels of DNA-PK and MGMT. Maslinic acid reduced the number of viable HeLa cells by inducing DNA damage and altering the expression of proteins involved in DNA damage and repair.

Chloroform extract of Citrus unshiu Markovich peel induces apoptosis and inhibits stemness in HeLa human cervical cancer cells

Cervical cancer is the second most common cancer among women worldwide. However, chemotherapies for this cancer often cause many side effects and chemoresistance. Citrus unshiu Markovich peel (CECU) has been used as a traditional medicine for the treatment of various diseases in East Asia. Recently, the anticancer activities and mechanisms of action of CECU extract have been reported in a number of different cancer cell types, but no study has evaluated the therapeutic effect of this natural product on cervical cancer cells. In the current study, the anticancer activity and the underlying molecular mechanism of the chloroform extract of CECU was investigated on HeLa human cervical cancer cells. The results showed that CECU effectively inhibited the proliferation and migration of HeLa cells. Treatment of cells with CECU led to cell cycle arrest at the G2/M phase and activation of extrinsic and intrinsic apoptotic pathways. Furthermore, the proliferation inhibitory effect of CECU was due to the inactivation of AKT and ERK signaling, upregulation of p53 and p21, and downregulation of cyclin B1 and cyclin D1, but not reactive oxygen species (ROS) generation. Furthermore, CECU inhibited the stem-like features of HeLa cells by downregulating key cancer stemness biomarkers. Therefore, CECU may be an effective complementary and alternative medicine for the prevention and treatment of cervical cancer.

JDP2 is directly regulated by ATF4 and modulates TRAIL sensitivity by suppressing the ATF4-DR5 axis.

Jun dimerization protein 2 (JDP2) is a bZip-type transcription factor, which acts as a repressor or activator of several cellular processes, including cell differentiation and chromatin remodeling. Previously, we found that a stress-responsive transcription factor, known as activating transcription factor 4 (ATF4), enhances JDP2 gene expression in human astrocytoma U373MG and cervical cancer HeLa cells; however, the role of JDP2 in the ATF4-mediated stress response remained unclear. Here, we reported that siRNA-mediated JDP2 knockdown enhances the expression of several ATF4 target genes, including ASNS, and death receptors 4 and 5 (DR4 and DR5) in HeLa cells. In addition, the results of a transient reporter assay indicate that JDP2 overexpression represses ER stress-mediated DR5 promoter activation suggesting that JDP2 negatively regulates ATF4-mediated gene expression. Curiously, knockdown of JDP2 increases the sensitivity of cells to TNF-related apoptosis-inducing ligand (TRAIL), which induces apoptosis in cancer cells through DR4 and DR5. These results indicate that JDP2 functions as a negative feedback regulator of the ATF4 pathway and contributes to TRAIL resistance in cancer cells.

Synthesis of CuO samples by co-precipitation and green mediated combustion routes: Comparison of their structural, optical properties, photocatalytic, antibacterial, haemolytic and cytotoxic activities

The goal of this research is to prepare novel, inexpensive, environment friendly and efficient crystalline CuO samples by green mediated combustion and co-precipitation routes towards environmental remediation and biomedical applications. The influence of preparation routes and Aloe barbadensis miller (Aloe vera) gel on the morphology, size, crystallinity, band gap, defects, photocatalytic, antibacterial, haemolytic and anticancer behaviour of CuO samples were explored. The PXRD, XPS, SEM, TEM, HRTEM and FT-IR were performed to confirm the formation of CuO samples. FTIR studies showed all possible bands of Aloe barbadensis miller gel. FTIR displaying the occurrence of new peaks and peak shifts in the CuO synthesized by green mediated combustion route compared to co-precipitation route is an evidence of the effective interactions between CuO and Aloe vera gel. The PL and UV–Vis-DRS techniques measured the optical sensitivity and tuning of band gap of the CuO samples. The crystallinity and surface properties dependent photocatalytic activities for decolourization of MB and RhB under both UV and Sunlight irradiation were investigated. The results indicated that green mediated synthesized CuO sample displayed high photocatalytic activity compared with co-precipitation route synthesized CuO sample, which mainly resulted from the low crystallinity and crystallite size (6 nm), narrow band gap (1.73 eV) and lower recombination of charge carriers. These synthesized CuO samples also demonstrate excellent antibacterial activity against the bacteria Gram-positive (S. aureus) and Gram-negative (E. coli). The present study probes into the cytotoxicity of CuO samples employing root cells of Allium cepa. In addition, we report the haemolytic activity on goat and human blood along with the implementation of green synthesized CuO sample using an Aloe barbadensis miller extract for the evaluation of anticancer activity in human cervical cancer (HeLa) cells with IC50 value of 310.1 μg/ml. Our studies focus on developing biosynthesized nanomaterials for environmental remediation and biomedical applications.

Tripartite motif‑containing14 regulates cell proliferation and apoptosis in cervical cancer via the Akt signaling pathway.

Tripartite motif-containing (TRIM) 14 is a protein of the TRIM family. Studies have indicated that TRIM14 may be used as an oncogene in tumor cells, such as osteosarcoma, non-small cell lung cancer and breast cancer through different pathways. However, the functions of TRIM14 in cervical cancer cells remain unclear. Therefore, this study aimed to investigate the functions of TRIM14 in cervical cancer cells and its underlying mechanism. Caski cells stably expressing TRIM14 and SiHa, and HeLa cells stably expressing TRIM14 short hairpin RNA were constructed by lentivirus-mediated overexpression or knockdown systems. The effects of TRIM14 on proliferation and apoptosis of cervical cancer cells were detected by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. In addition, reverse transcription-quantitative (RT-q) PCR and western blotting were used to investigate the expression levels of TRIM14 and of signaling pathway marker protein including P21, caspase-3, cleaved caspase-3, Akt and phosphorylated Akt. The results of RT-qPCR and western blotting revealed that TRIM14 was highly expressed in human cervical cancer tissues and cell lines compared with adjacent normal tissues and normal cervical epithelial cells. TRIM14 also regulated cell proliferation and apoptosis of human SiHa, HeLa and Caski cervical cancer cell lines through the Akt signaling pathway. Additionally, TRIM14 protein levels were related to the clinical and pathological features of cervical cancer. CCK-8 assay and flow cytometry demonstrated that TRIM14 expression could promote cervical cancer cell proliferation and autophagy suppression. Taken together, TRIM14-induced cell proliferation and apoptosis inhibition may by evoked by the activation of the Akt pathway. This study demonstrated the role of TRIM14 in cervical cancer, and reveals its mechanism of action as a potential therapeutic target for cervical cancer.

Chemical constituents and absolute configuration of megastigmanes’ isolated from Sedum sarmentosum Bunge

Phytochemical investigation of a methanolic extract of Sedum sarmentosum collected from Vietnam resulted in the isolation of a new megastigmane glucoside, named sedumoside K (1), together with 17 previously reported compounds (2–18). Structural elucidation of the new compound was achieved by HRFABMS, NMR spectroscopic analysis, acid hydrolysis and quantum ECD calculations. The absolute configuration of compounds 2–6 has been revised. The major isolates were tested for cytotoxic activity against HeLa human cervical cancer cells, and all showed moderate activities.

Direct Transfer of Mesoporous Silica Nanoparticles between Macrophages and Cancer Cells.

Simple SummaryA challenge for Nanomedicine is delivery to the site of action, most commonly the tumor microenvironment. When injected systemically, scavenger cells, such as macrophages, rapidly sequester nanoparticles. This study asks if macrophages can directly deliver scavenged nanoparticles to cancer cells via cellular connections known as tunneling nanotubes. Knowledge of the in vivo cellular fate of nanoparticles is critical for the design of optimized nanocarriers for clinical translation.Macrophages line the walls of microvasculature, extending processes into the blood flow to capture foreign invaders, including nano-scale materials. Using mesoporous silica nanoparticles (MSNs) as a model nano-scale system, we show the interplay between macrophages and MSNs from initial uptake to intercellular trafficking to neighboring cells along microtubules. The nature of cytoplasmic bridges between cells and their role in the cell-to-cell transfer of nano-scale materials is examined, as is the ability of macrophages to function as carriers of nanomaterials to cancer cells. Both direct administration of nanoparticles and adoptive transfer of nanoparticle-loaded splenocytes in mice resulted in abundant localization of nanomaterials within macrophages 24 h post-injection, predominately in the liver. While heterotypic, trans-species nanomaterial transfer from murine macrophages to human HeLa cervical cancer cells or A549 lung cancer cells was robust, transfer to syngeneic 4T1 breast cancer cells was not detected in vitro or in vivo. Cellular connections and nanomaterial transfer in vivo were rich among immune cells, facilitating coordinated immune responses.

(η6-Arene) ruthenium(II) complexes with ferrocene-tethered salicylaldimine ligands: Synthesis, characterization and anti-cancer properties

A series of ruthenium(II) complexes (5a-5f) derived from ferrocenyl salicylaldimine ligands (3a-3f), coordinated in a chelating mode through the deprotonated phenolic oxygen atom and the imine nitrogen, were synthesized and fully characterised. The molecular structures of selected ligands and complexes were also confirmed by X-ray diffraction analysis. The heterobimetallic Ru-Fe complexes 5a-5f were evaluated for their in vitro anti-cancer activity against human liver cancer (HepG2) and human cervical cancer (HeLa) cell lines and showed better activities compared to the ferrocenyl salicylaldimine ligands. Among the heterobimetallic complexes, 5c and 5d showed enhanced cytotoxicity against HeLa cancer cells (IC50 value of 9.34 µM compared to 31.32 µM for cisplatin), and HepG2 cancer cells (IC50 value of 15.74 µM compared to 27.95 µM for cisplatin), respectively. Mechanistic studies indicated compound 5d induced cell cycle arrest in the S phase. Further, compound 5d treatment resulted in increased ROS generation and loss of mitochondrial membrane potential in HepG2 cells.

Protein interaction and in vitro cytotoxicity studies of newly designed palladium (II) nitrate complexes: spectrochemical, theoretical and biological assessments

The biological assessments of new synthesized palladium (II) complexes [1, 10-phenanthroline hexyl dithiocarbamato palladium (II) nitrate (complex I), and 1, 10-phenanthroline butyl dithiocarbamato palladium (II) nitrate (complex II)] were investigated using in vitro cytotoxicity and molecular interaction studies. The in vitro cytotoxicity studies were done against human cervical HeLa cancer cell line and human breast MDA-MB-468 cancer cell line. The interaction evaluations were done using human hemoglobin (Hb) as the primary target of novel palladium (II) complexes using spectroscopy methods of fluorescence and circular dichroism at various temperatures of 25, 37, 42, and 47 °C as well as molecular docking. The results have indicated complex I and complex II are quite similar in functionality. They induced apoptotic cell death so that they showed a significant growth inhibitory effect against HeLa and MDA-MB-468 cells. The fluorescence spectroscopy and molecular docking indicated that there is only one binding site for new palladium (II) complexes on Hb. The interaction studies revealed complex I and complex II have the same structural effects and similar binding properties on Hb. Finally, the results showed the newly synthesized palladium (II) complexes have no structural degradation on Hb. Therefore, they can be introduced as promising candidates in cancer treatment.

Cytotoxicity Potential of Endophytic Fungi Extracts from Terminalia catappa against Human Cervical Cancer Cells.

Endophytic fungi are potential sources of novel bioactive metabolites from a natural product drug discovery perspective. This study reports the bioactivity-directed fractionation of the secondary metabolites of the ethyl acetate extract of a fermentation culture of endophytic fungi from Terminalia catappa which were then evaluated for their cytotoxicity against human cervical cancer (HeLa) cells and human foreskin fibroblast (HFF) cells. Furthermore, apoptosis was determined using the Annexin V/propidium iodide (PI) flow cytometry assay. Endophyte extracts N2, N7, N8, N97, N169, and N233 were obtained from Trichoderma sp, Phoma sp, Phomopsis phyllanticola, Fusarium oxyporum, Collectotrichum sp, and Cryptococcus flavescens, respectively. The N97 extract was most active with a 50% inhibitory concentration (IC50) of 33.35 µg/ml. A 50% cytotoxic concentration (CC50) of 268.4 µg/ml was obtained with HFF cells and the selectivity index (SI) was 8.01. The percentages of cell populations were increased at late apoptosis (Annexin+/PI+), with the percentages of 27.4 ± 0.3 and 19.2 ± 0.01 obtained, respectively, for 50 µg/ml and 80 µg/ml of the N97 extract and 2.1 ± 0.1 obtained for the control in late apoptosis (Annexin V+/PI+) . Moreover, a higher reduction in the percentage of viable cells was observed in the HeLa control cells (93.6 ± 0.3), but the percentages of viable HeLa cells were 37 ± 0.05 and 45 ± 0.1, respectively, for the 50 µg/ml and 80 µg/ml treatments with the N97 extract. Also, the percentages of 34.7 ± 0.1 and 33.9 ± 0.4 were, respectively, obtained for 50 µg/ml and 80 µg/ml compared to the control with 4.6 ± 0.2, in early apoptosis (Annexin V+/PI-). These findings highlight the anticancer potential of the N97 extract of endophytic fungi from Terminalia catappa, which is mediated through apoptosis and presumably also attenuation of chemoresistance.