Growth Of HeLa Cells Research Articles

Beyond Chemistry: Investigating the Physical, Pharmacological, and Computational Aspects of Polyoxometalate Integrated Solid Lipid Nanoparticles for Cancer Treatment.

The solid lipid nanoparticles of transitional metal complexes (POMs) were prepared with natural lipids with the aim of developing a safer therapeutic approach for cancer treatment. Natural lipids were used to create solid lipid nanoparticles containing transitional metal complexes (POMs). The nanoparticles had displayed appreciable entrapment and loading percentage of P5W30. The zeta capacitance was measured to be -32.57±6.44 mV with average particle dimension of 160.5±8.61 nm and polydispersity index (PDI) of around 0.3814±0.096. The effectiveness of P5W30-BW-SLNs in inhibiting the growth of HeLa cells was found to be higher (IC50 = 3.02±2.14µg/mL) compared to pure P5W30 (IC50 = 7.93±5.08µg/mL). Further examinations of DNA damage were made through comet test and flow cytometry techniques. The assessment of tumor regression and survival was conducted, and comparison was recorded. The P5W30-BW-SLNs resulted in a 72.91% increase in survival rates and a reduction in tumor burden by 2.967±0.543%. Moreover, the computational findings demonstrate a strong connection with the actual data, providing a plausible explanation for the notable chemopreventive efficacy of POM against HeLa cell lines. The study's findings might pave the way for a more efficient delivery system in cancer treatment.

Violaceoid F induces nuclear translocation of FOXO3a by inhibiting CRM1 via a novel mechanism and suppresses HeLa cell growth.

FOXO3a is a transcription factor involved in cell growth inhibition and apoptosis. FOXO3a is localized in the cytoplasm in cancer cells, and its nuclear translocation by small molecules is expected to prevent cancer cell growth. In this study, we screened a fungal broth library in HeLa cells using fluorescently labeled FOXO3a and an AI-based imaging system. We identified violaceoid F, which translocates FOXO3a into the nucleus by inhibiting CRM1, which is responsible for nuclear protein export. Violaceoid F was observed to target the reactive cysteine of CRM1 through its α, β-epoxyketone. However, because violaceoid F did not inhibit Crm1 in fission yeast cells, it seems to target cysteine residue(s) other than Cys528 of human CRM1 which are not targeted by other known CRM1 inhibitors, indicating that violaceoid F inhibits CRM1 via a novel mechanism.

A Zeolitic Imidazolate Framework-Based Antimicrobial Peptide Delivery System with Enhanced Anticancer Activity and Low Systemic Toxicity.

The clinical efficacies of anticancer drugs are limited by non-selective toxic effects on healthy tissues and low bioavailability in tumor tissue. Therefore, the development of vehicles that can selectively deliver and release drugs at the tumor site is critical for further improvements in patient survival. We prepared a CEC nano-drug delivery system, CEC@ZIF-8, with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta potential, infrared (IR), x-ray diffraction (XRD), and transcriptome analysis, and examined the in vitro cytotoxicity and cellular uptake properties of CEC@ZIF-8 using cervical cancer cells. Lastly, we established a TC-1 tumor-bearing mouse model and evaluated its in vivo anti-cervical cancer activity. The CEC@ZIF-8 nano-delivery system had favorable biocompatibility, heat stability, and pH responsiveness, with a CEC loading efficiency of 12%, a hydrated particle size of 174 ± 5.8 nm, a zeta potential of 20.57 mV, and slow and massive drug release in an acidic environment (pH 5.5), whereas release was 6% in a neutral environment (pH 7.4). At the same time, confocal imaging and cell viability assays demonstrated greater intracellular accumulation and more potent cytotoxicity against cancer cells compared to free CEC. The mechanism was analyzed by a series of transcriptome analyses, which revealed that CEC@ZIF-8 NPs differentially regulate the expression levels of 1057 genes in cancer cells, and indicated that the enriched pathways were mainly cell cycle and apoptosis-related pathways via the enrichment analysis of the differential genes. Flow cytometry showed that CEC@ZIF-8 NPs inhibited the growth of HeLa cells by arresting the cell cycle at the G0/G1 phase. Flow cytometry also revealed that CEC@ZIF-8 NPs induced greater apoptosis rates than CEC, while unloaded ZIF-8 had little inherent pro-apoptotic activity. Furthermore, the levels of reactive oxygen species (ROS) were also upregulated by CEC@ZIF-8 NPs while ROS inhibitors and caspase inhibitors reversed CEC@ZIF-8 NPs-induced apoptosis. Finally, CEC@ZIF-8 NPs also reduced the growth rate of xenograft tumors in mice without the systemic toxicity observed with cisplatin treatment. The CEC@ZIF-8 nano-drug delivery system significantly enhanced the anti-cervical cancer effect of CEC both in vivo and in vitro, providing a more promising drug delivery system for clinical applications and tumor management. At the same time, this work demonstrates the clinical potential of CEC-loaded ZIF-8 nanoparticles for the selective destruction of tumor tissues.

Investigation of the Apoptotic and Antimetastatic Effects of Nano-Niosomes Containing the Plant Extract Anabasis setifera on HeLa: In Vitro Cervical Cancer Study.

The present study focuses on the preparation of niosomes containing an extract of Anabasis setifera and evaluates their efficacy in inhibiting the growth and proliferation of HeLa cells. Thin-layer hydration technique was used to prepare niosomes/extract nanoparticles (NPs). The physicochemical properties of the synthesized NPs were confirmed by scanning electron microscope (SEM), dynamic light scattering (DLS), zeta potential analysis, and FTIR. The cytotoxicity of the free extract, free niosome, and NPs was investigated by MTT (3-(4, 5-diMethylThiazol-2-yl)-2,5-diphenylTetrazolium bromide) assay. For this purpose, solutions of the three mentioned agents were prepared and diluted in 400, 200, 100, 50, 25, 12.5, and 6.25µg/mL concentrations and incubated for 24, 48, and 72h. After calculating the IC50 concentration and treating the cells with this concentration, real-time polymerase chain reaction (PCR) (to measure changes in the expression of apoptosis and metastasis genes), flow cytometry (to determine the amount of early and late induced apoptosis), and cell cycle test (to determine the stopping stage of the cancer cell division cycle) were performed. Moreover, the scratch test (the ability to inhibit cell metastasis after treatment) was used to evaluate cell migration. The MTT assay results showed that 72h of treatment with NPs has the greatest effect on the death of cancer cells. Real-time PCR showed that the expression of the Bad gene increased dramatically and the expression of the BCL-XL, integrin alpha 5 (ITGA5), and zinc finger E-box-binding homeobox 1 (ZEB-1) genes decreased significantly. The flow cytometry results showed that 48.64% of HeLa cells underwent apoptosis after treatment with synthesized NPs. The scratch test results showed that cancer cell metastasis stopped after treatment with NPs. The research demonstrates the significant potential of plant extract-loaded niosomes, as highly efficient drug carriers for cancer therapy.

Tripodal Quinone-Cyanine G-Quadruplex Ligands as Novel Photosensitizers on Photoinduced Cancer Cell Death.

Guanine-quadruplex (G4) selective photosensitizers have huge potential for photodynamic therapy against various diseases correlated with G4 DNA and G4 RNAs; however, the types of photosensitizer skeletons available are limited. Herein, we investigated the ability of our original G4 ligands, tripodal quinone-cyanine dyes (tpQCy(s)), which were developed as fluorescent probes for G4, to act as photosensitizers for cancer-selective apoptosis inducers. The results indicated that the tpQCy skeleton has great potential for developing G4-targeted cancer-selective photosensitizers for photodynamic therapy. Among the two tpQCys, only QCy(BnBT)3, which has greater G4 selectivity, exhibited photoinduced cytotoxicity in HeLa cell growth, suggesting that the direct oxidation of G4 DNA or RNA is crucial for photoinduced cytotoxicity. RNA-seq analysis using a next-generation sequencing technique revealed that apoptosis was clearly induced by photoirradiation after QCy(BnBT)3 treatment.

Mechanism of autophagy inhibition for sensitizing HeLa cell apoptosis induced by trichosanthin

This research investigated the effect and mechanism of trichosanthin(TCS) in inducing autophagy and apoptosis of HeLa cells in cervical cancer. Two-step chromatography was used to prepare TCS. MTT assay was used to detect the inhibition effect of TCS on the proliferation of HeLa cells. The formation of autophagic vesicles and apoptotic bodies in HeLa cells treated with TCS was observed under transmission electron microscopy, and green fluorescent protein(GFP)-microtubule-associated protein 1 light chain beta 3(LC3B) fusion protein location was observed under laser confocal microscopy. The expression of autophagy and apoptosis-related proteins was detected by Western blot. It was found that the prepared TCS had high purity and biological activity. TCS could inhibit the proliferation of HeLa cells significantly in a concentration-dependent and time-dependent manner. Obvious autophagic vesicles were observed after HeLa cells were treated with TCS for 12 h, and typical apoptotic bodies were formed after 48 h. Under laser confocal microscopy, LC3B protein was observed to shift from a diffuse distribution to a spotted aggregation distribution in the cytoplasm. Western blot results showed that the expression of autophagy-activating protein LC3BⅡ began to increase in HeLa cells after being treated with TCS for 12 h and increased with the increase in drug concentration. Apoptosis-related protein poly ADP-ribose polymerase(PARP) began to activate as cleaved PARP after being treated with TCS for 24 h. The combination of TCS and 3-methyladenine(3-MA) further promoted the activation of cleaved PARP. The results showed that TCS could significantly inhibit the growth of HeLa cells in cervical cancer. Moreover, TCS induced autophagy in HeLa cells earlier than apoptosis, and inhibiting autophagy could sensitize apoptosis of HeLa cells induced by TCS. This indicated that autophagy induced by TCS was a protective cell response, and TCS combined with autophagy inhibitors could enhance the anti-cervical cancer effect of TCS.

Synthesis, characterization and anticancer, antibacterial activities of pentacyclic triterpenoid glycoside derivatives

As a kind of glycoside, pentacyclic triterpenoid saponins have good biological activities, such as anticancer, antibacterial, antiviral and hypoglycemic effects [1]. In this paper, twenty-four pentacyclic triterpenoid derivatives, including twelve monosaccharide derivatives, were designed and synthesized. The anticancer effect and antibacterial activities of all compounds were evaluated. It is noteworthy that compound UA-2b has the strongest inhibitory effect on the growth of A549, Hela and HepG2 cancer cells (IC50 = 5.37 ± 0.22 µM, 5.82 ± 0.25 µM and 5.47 ± 0.06 µM, respectively). Compounds OA-2b, OA-6a, OA-6b, UA-2b and UA-6a have the best activity against Escherichia coli 1924 (MIC = 16 μg/ml).

Differential effects of enzymatically modified Ougan (Citrus Suavissima Hort. ex Tanaka) peel pectins extracted with different methods on inhibiting the proliferation of Hela cells

Previous studies have shown that modified citrus pectin (MCP) is an anti-tumor material of food grade. In this study, two enzymatically modified Ougan (Citrus Suavissima Hort. ex Tanaka) peel pectins (EMP1 and EMP2, the ones extracted by alkali and enzymatic methods) were used to investigate their differential effects on viability and physiology of Hela cells. The results showed that EMP1 and EMP2 had 88.00 % and 81.01 % galacturonic acid, 21.31 % and 20.25 % esterification degree, 10,417 g/mol and 6416 g/mol molecular weight (Mw), 82.86 % and 50.62 % RG-I, and 8.91 % and 15.70 % HG, respectively. EMP2 had higher intensities of absorption peaks than EMP1. They were irregularly shaped, with more holes on EMP1 but more wrinkles on EMP2. Both could inhibit the growth, proliferation, migration, and invasion of HeLa cells in a concentration-dependent manner, with better efficiency in EMP2. Meanwhile, EMP2 was more efficient than EMP1 in blocking the cell cycle in S phase, resulting in apoptosis. In conclusion, the variations caused by extraction resulted in differences in anti-tumor activity of MCP and EMP2 with lower Mw and higher HG exhibited better anti-tumor effects. This study would provide an experimental basis and reference for the research and development of anti-tumor supplements from citrus pectin.

Anticancer Potential of Valencia Peanut (Arachis hypogaea L.) Skin Extract against Cervical Cancer Cells In Vitro and in Nude Mouse Xenograft Models.

This study investigated the impact of Valencia KK4-type peanut skin ethanolic extract (KK4-PSE) combined with cisplatin or 5-fluorouracil (5-FU) on HeLa cells in vitro and in xenograft models. At exposure times of 24, 48 and 72 h, KK4-PSE inhibited the growth of HeLa cells with a half maximal inhibitory concentration (IC50) of 79.43 ± 0.54, 55.55 ± 1.57 and 41.32 ± 0.74 µg/mL, respectively. Drug interactions evaluated by the Chou-Talalay method demonstrated that KK4-PSE enhanced antiproliferative activity of 5-FU against HeLa cells with combination index (CI) values of 0.49 (48 h) and 0.60 (72 h), indicating a synergistic effect, while KK4-PSE combined with cisplatin exhibited an additive effect (CI = 1.02) at 72 h, and an antagonistic effect at 24 and 48 h exposures (CI = 1.12 and 1.18, respectively). In nude mouse xenograft models, the combination of 5-FU and KK4-PSE markedly reduced HeLa tumor weights compared with the control and single agent treatments groups. The combination of KK4-PSE and 5-FU achieved greater tumor growth inhibition than that of the KK4-PSE-cisplatin combination. KK4-PSE mitigated hepatotoxicity induced by both cisplatin and 5-FU in nude mice. The spleen hyaloserositis was significantly reduced in the combination treatment of 5-FU and KK4-PSE. These results suggest that KK4-PSE has the potential to limit cervical cancer cell proliferation while reducing the toxicity of cisplatin and 5-FU.

Vaginal Ovule Loaded with Bismuth Lipophilic Nanoparticles and Cetylpyridinium Chloride Inhibits Human Cervical Carcinoma and Candida albicans Growth.

Bismuth lipophilic nanoparticles (BisBAL NPs) and cetylpyridinium chloride (CPC) are antineoplastic and antimicrobial in vitro. As a next pre-clinical step, a clinically viable dosage form for vaginal application was developed. Compendial pharmacopeial tests (mass uniformity, disintegration, and compressive mechanics) and inductively coupled plasma optical emission spectroscopy were conducted on in-house developed glycerinated gelatin (60:15 v/w) vaginal ovules containing BisBAL NP-CPC. The antimycotic activity of BisBAL NP-CPC vaginal ovules was analyzed using disk diffusion and cell viability XTT assays. The antitumor properties of BisBAL NP-CPC vaginal ovules were assessed by cell viability MTT tests. BisBAL NP-CPC and drug-free vaginal ovules deposited into ex vivo porcine vaginas disaggregated without signs of adverse cytotoxicity within the timespan of clinical efficacy. BisBAL NP-CPC vaginal ovules demonstrated antifungal efficacy comparable to miconazole: C. albicans growth inhibition haloes in diffusion tests were 23 ± 0.968 mm (n = 3) for BisBAL NP-CPC and 20.35 ± 0.899 mm (n = 3) for miconazole. Likewise, BisBAL NP-CPC vaginal ovules reduced HeLa cell growth by 81%, outperforming the clinical reference of 500 μM 5-fluouracil, which induced a 70% growth inhibition. BisBAL NP-CPC incorporated into glycerinated gelatin vaginal ovules constitute an innovative drug delivery system for topical antimycotic and anti-cervical carcinoma treatments.

Two undescribed constituents from Salvia castanea Diels and evaluation of their cytotoxic activity

One previously undescribed abietane diterpene alkaloid containing an oxazole ring (1), one unreported abietane diterpene (2), and nine known abietane diterpenes (3–11) were isolated from the roots and rhizomes of Salvia castanea Diels. Their structures and absolute configurations were elucidated by a combination of HRESIMS, 1D and 2D NMR, and ECD. All compounds were evaluated for their cytotoxic activity against several human cancer cell lines (HepG2, A549, H460, MCF7, PC3, and Hela). The results showed that 1 exhibited a moderate cytotoxic effect on HepG2 cells (IC50: 14.22 ± 1.05 μM) and was able to inhibit the cell growth of MCF7 and Hela cells by 35.08% and 47.26% respectively, at a concentration of 20 μM, while other compounds showed low cytotoxic activity.

Fabrication and characterization of unique sustain modified chitosan nanoparticles for biomedical applications

Chitosan (CS) is a biopolymer that offers a wide range in biomedical applications due to its biocompatibility, biodegradability, low toxicity and antimicrobial activity. Syringaldehyde (1) is a naturally occurring organic compound characterized by its use in multiple fields such as pharmaceuticals, food, cosmetics, textiles and biological applications. Herein, development of chitosan derivative with physicochemical and anticancer properties via Schiff base formation from the reaction of chitosan with sustainable eco-friendly syringaldehyde yielded the (CS-1) derivative. Moreover, in the presence of polyethylene glycol diglycidyl ether (PEGDGE) or sodium tripolyphosphate (TPP) as crosslinkers gave chitosan derivatives (CS-2) and (CS-3NPs) respectively. The chemical structures of the new chitosan derivatives were confirmed using different tools. (CS-3NPs) nanoparticle showed improvement in crystallinity, and (CS-2) derivative revealed the highest thermal stability compared to virgin chitosan. The cytotoxicity activity of chitosan and its derivatives were evaluated against HeLa (human cervical carcinoma) and HEp-2 (Human Larynx carcinoma) cell lines. The highest cytotoxicity activity was exhibited by (CS-3NPs) compared to virgin chitosan against HeLa cell growth inhibition and apoptosis of 90.38 ± 1.46% and 30.3% respectively and IC50 of 108.01 ± 3.94 µg/ml. From the above results, it can be concluded that chitosan nanoparticle (CS-3NPs) has good therapeutic value as a potential antitumor agent against the HeLa cancer cell line.

Chondroitin sulfate-functionalized selenium nanoparticle-induced S-phase cell cycle arrest and apoptosis in HeLa Cells.

This study aimed to evaluate the anti-cervical cancer activity of chondroitin sulfate-functionalized selenium nanoparticles (SeCS) and to elucidate their action mechanism. Cytotoxic effect of SeCS on HeLa cells was assessed by MTT assay. Further molecular mechanism of SeCS was analyzed by flow cytometric assay and western blotting. The results showed that treatment with SeCS resulted in a dose- and time-dependent inhibition in the proliferation of HeLa cells. The data obtained from flow cytometry demonstrated that SeCS inhibited HeLa cell growth via the induction of S-phase arrest and cell apoptosis. Further mechanism analysis found that SeCS down-regulated expression levels of cyclin A and CDK2 and up-regulated p21 expression, which contributed to S arrest. Moreover, SeCS increased the level of Bax and decreased the expression of Bcl-2, resulting in the release of cytochrome C from mitochondria and activating caspase-3/8/9 for caspase-dependent apoptosis. Meanwhile, intracellular reactive oxygen species (ROS) levels were elevated after SeCS treatment, suggesting that ROS might be upstream of SeCS-induced S-phase arrest and cell apoptosis. These data show that SeCS has anti-tumor effects and possesses the potential to become a new therapeutic agent or adjuvant therapy for cancer patients. PRACTICAL APPLICATION: In our previous study, we used chondroitin sulfate to stabilize nano-selenium to obtain SeCS to improve the bioactivity and stability of nano-selenium. We found that it possessed an inhibitory effect on HeLa cells. However, the molecular mechanism remains unclear. This study elucidated the mechanism of SeCS damage to HeLa cells. SeCS has the potential to become a new therapeutic agent or adjuvant therapy for cancer patients.

LINC01605 promotes malignant phenotypes of cervical cancer via miR-149-3p/WNT7B axis

BackgroundLong non-coding RNAs (LncRNA) play a pivotal role in the progression of various malignancies. Despite recent identification as an oncogene associated with tumorigenesis. The precise role of LINC01605 in cervical cancer (CC) remains unclear. Therefore, the objective of this study was to investigate the influence of LINC01605 on proliferation and invasion of CC cells, while also exploring its potential underlying mechanisms. MethodsThe expression of LINC01605 in CC cell lines was analyzed using the TCGA database and qRT-PCR. Various assays, including CCK-8 and transwell analysis, were conducted on CC cells to assess the influence of LINC01605 on their proliferation, migration, and invasion capabilities. Bioinformatics and dual luciferase reporter gene assays were employed to analyze the target genes of LINC01605 and miR-149-3p. To further investigate the mechanism of action, transfection and investigation were performed using specific siRNA, miRNA mimics, or inhibitors. ResultsThe expression of LINC01605 exhibited a significant increase in CC cell lines, and this upregulation was associated with an unfavorable prognosis. Modulating the expression of LINC01605, either by down-regulating or up-regulating it, exerted suppressive or stimulatory effects on the growth and invasion of HeLa and Siha cells. LINC01605 functioned as a competitive endogenous RNA (ceRNA) for miR-149-3p, with WNT7B being identified as a target gene of miR-149-3p. The involvement of LINC01605 in CC development is facilitated by its ability to regulate the expression of WNT7B through sequestering miR-149-3p. ConclusionOur study demonstrates that LINC01605 acts as a competitive endogenous RNA in modulating the effects of WNT7B on the proliferation and invasion of CC cells by sequestering miR-149-3p. This research provides novel insights into the involvement of LINC01605 in the advancement of CC.

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.

Nuclear deformation and cell division of single cell on elongated micropatterned substrates fabricated by DMD lithography

Cells sense mechanical signals from the surrounding environment and transmit them to the nucleus through mechanotransduction to regulate cellular behavior. Microcontact printing, which utilizes elastomer stamps, is an effective method for simulating the cellular microenvironment and manipulating cell morphology. However, the conventional fabrication process of silicon masters and elastomer stamps requires complex procedures and specialized equipment, which restricts the widespread application of micropatterning in cell biology and hinders the investigation of the role of cell geometry in regulating cell behavior. In this study, we present an innovative method for convenient resin stamp microfabrication based on digital micromirror device planar lithography. Using this method, we generated a series of patterns ranging from millimeter to micrometer scales and validated their effectiveness in controlling adhesion at both collective and individual cell levels. Additionally, we investigated mechanotransduction and cell behavior on elongated micropatterned substrates. We then examined the effects of cell elongation on cytoskeleton organization, nuclear deformation, focal adhesion formation, traction force generation, nuclear mechanics, and the growth of HeLa cells. Our findings reveal a positive correlation between cell length and mechanotransduction. Interestingly, HeLa cells with moderate length exhibit the highest cell division and proliferation rates. These results highlight the regulatory role of cell elongation in mechanotransduction and its significant impact on cancer cell growth. Furthermore, our methodology for controlling cell adhesion holds the potential for addressing fundamental questions in both cell biology and biomedical engineering.

Dictyostelium Differentiation-Inducing Factor 1 Promotes Glucose Uptake via Direct Inhibition of Mitochondrial Malate Dehydrogenase in Mouse 3T3-L1 Cells.

Differentiation-inducing factor 1 (DIF-1), found in Dictyostelium discoideum, has antiproliferative and glucose-uptake-promoting activities in mammalian cells. DIF-1 is a potential lead for the development of antitumor and/or antiobesity/antidiabetes drugs, but the mechanisms underlying its actions have not been fully elucidated. In this study, we searched for target molecules of DIF-1 that mediate the actions of DIF-1 in mammalian cells by identifying DIF-1-binding proteins in human cervical cancer HeLa cells and mouse 3T3-L1 fibroblast cells using affinity chromatography and liquid chromatography-tandem mass spectrometry and found mitochondrial malate dehydrogenase (MDH2) to be a DIF-1-binding protein in both cell lines. Since DIF-1 has been shown to directly inhibit MDH2 activity, we compared the effects of DIF-1 and the MDH2 inhibitor LW6 on the growth of HeLa and 3T3-L1 cells and on glucose uptake in confluent 3T3-L1 cells in vitro. In both HeLa and 3T3-L1 cells, DIF-1 at 10-40 μM dose-dependently suppressed growth, whereas LW6 at 20 μM, but not at 2-10 μM, significantly suppressed growth in these cells. In confluent 3T3-L1 cells, DIF-1 at 10-40 μM significantly promoted glucose uptake, with the strongest effect at 20 μM DIF-1, whereas LW6 at 2-20 μM significantly promoted glucose uptake, with the strongest effect at 10 μM LW6. Western blot analyses showed that LW6 (10 μM) and DIF-1 (20 μM) phosphorylated and, thus, activated AMP kinase in 3T3-L1 cells. Our results suggest that MDH2 inhibition can suppress cell growth and promote glucose uptake in the cells, but appears to promote glucose uptake more strongly than it suppresses cell growth. Thus, DIF-1 may promote glucose uptake, at least in part, via direct inhibition of MDH2 and a subsequent activation of AMP kinase in 3T3-L1 cells.

POTENTIAL KETAPANG (Terminalia cattapa) LEAF EXTRACT AS A DOXORUBICIN CO-CHEMOTHERAPY AGENT ON BREAST (T47D) AND CERVIX (HeLa) CANCER CELL LINES

Doxorubicin (DOX) is chemotherapy for breast and cervical cancer with serious side effects. Ketapang (Terminalia cattapa) is a potential plant as a co-chemotherapy agent. The purpose of this research was to examine the sensitivity of DOX as a cytotoxicity drug in combination with ethanolic extracts of ketapang leaves (EKL) against T47D and HeLa cancer cells. Cytotoxicity was determined using the MTT assay, with DOX concentration series (0.625-40 nM for T47D and 0.5-6 M for HeLa) and EKL (50-1000 mg/mL) used in combination with the study. DOX and EKL combination assays utilizing their respective IC50 values were performed in T47D cells and HeLa cells, and the results were used to calculate the Combination Index (CI). Furthermore, the doubling time method was used to investigate the combination of DOX and EKL proliferation inhibition on both cell lines. DOX and EKL had IC50 values of 158 nM and 30 mg/mL for T47D, respectively, and 3.4 M and 640 mg/mL for HeLa cell growth. While DOX and EKL have a synergistic effect on T47D cells, their combined effect on HeLa cells is cytotoxic and dose-dependent. EKL increases the inhibitory effect of DOX on the proliferation of T47D and HeLa cancer cells. In T47D cells, the combination of DOX and EKL has a higher potential for cytotoxic and antiproliferative activity than in HeLa cells

Exploring the therapeutic potential of edible vegetables, fruits, and spices against cancer in various cell lines.

Cancer is rapidly becoming the leading cause of death globally. This study aimed to identify edible foods with cytotoxic and/or antioxidant activities that can prevent cancer when consumed in a regular diet. Sixty-eight edible foods were purchased from the local market, and the materials were extracted with 80% methanol. The cytotoxic activity of the extracts was evaluated using MTT on HeLa, H2228, HEK293, and H3122 cell lines. To study apoptosis, triple fluorescence labeling with DAPI, Annexin V, and propidium iodide was used. The phenolic content, antioxidant capacity, and free radical scavenging capabilities were studied using conventional spectrophotometric techniques. Among the edible foods, carrot, pointed gourd, wax gourd, ficus, apple, lemon, cumin seed, and white peppercorn showed moderate cytotoxicity in HeLa cells. The growth of HeLa cells was significantly inhibited dose-dependently by tomato, banana, Indian spinach, guava, lemon peel, and coriander (IC50, 24.54, 17.89, 13.18, 9.33, 1.23, and 2.96 µg/mL, respectively). Tomato, Indian spinach, lemon peel, and coriander exerted significant dose-dependent inhibition of H2228, HEK293, and H3122 cell proliferation. The tomato, Indian spinach, lemon peel, and coriander extracts induced HeLa cell apoptosis. White peppercorn, amaranth, apple, wax gourd, cumin seed, taro, and lemon peel contained significant amounts of polyphenols and showed high antioxidant activity. White peppercorn, apple, coriander, lemon peel, and ficus significantly scavenged DPPH free radicals (IC50 values of 10.23, 12.02, 13.49, 13.8, and 14.0 µg/mL, respectively). The overall results suggest that the daily intake of these antioxidant-rich cytotoxic foods can prevent or reduce the risk of cancer.

Mixed ligand Ni(II) complexes containing 2-chloroquinoline-3-carboxaldehyde-4(N)-substituted thiosemicarbazones and 2,2′-bipyridine: Synthesis, spectral characterization and in-vitro cytotoxicity

Ni(II) complexes (NiL1-NiL4) of 2-chloroquinoline-3-carboxaldehyde-4(N)-substituted thiosemicarbazones and 2,2′-bipyridine ligands were prepared and characterized by various spectroscopic techniques such as Fourier Transform Infrared (FT-IR), Ultraviolet–visible (UV–vis), 1H NMR and mass spectroscopy. The binding of the ligands to the nickel ion was through their azomethine nitrogen and thiolate sulfur atoms. The redox properties of the complexes were analyzed by cyclic voltammetry. The binding affinity of the complexes with CT-DNA (Calf Thymus DNA) and BSA (Bovine Serum Albumin) was studied using absorption and emission methods. The complex NiL3 exhibited better binding activity with high binding constant value with both DNA and BSA. Antiproliferative ability of the Ni(II) complexes (NiL1-NiL4) was explored against human cervical cancer cells HeLa and human normal embryonic kidney cells HEK. The morphological changes induced by the Ni(II) complexes on HeLa cells were analyzed by AO-EB and DAPI staining assays. The results obtained from the cytotoxicity studies showed the better cytotoxicity of the complex NiL3 towards inhibiting the growth of HeLa cells, whereas non toxic nature of the complexes was proved with HEK cells.