Cervical Carcinoma Cell Line HeLa Research Articles

Induction of Apoptotic Death and Cell Cycle Arrest in HeLa Cells by Extracellular Factors of Breast Cancer Cells

Background:There are evidences on the role of extracellular factors in cellular communication between cancer cells and non-cancerous cells to support tumor progression and a phenomenon of cancer cachexia. However, evidences are scarce to show the effects of extracellular factors from one carcinoma microenvironment upon growth and survival of another carcinoma.Methodology:To address the above issue, we have selected excised breast carcinoma tissue samples and in vitro grown MCF-7 sources of extracellular factors and tested their effects to evaluate growth and proliferation inhibitory potential against a cervical carcinoma cell line HeLa.Results:Data from the in vitro experiments like Trypan blue dye exclusion, MTT assay, cell cycle assay and annexin V/PI staining lead us to suggest that the extracellular factors collected from the culture medium of in vitro grown MCF-7 and excised breast carcinoma tissue play an apoptosis inducing and cell cycle arrest role in HeLa. In these in vitro experiments, we detected the presence of up to 40-50% apoptotic cell death in HeLa cells and increase in G2-M cell cycle phase from 11%-25% due to treatment with extracellular factors from human breast carcinoma cells.Discussion and Conclusion:These observations are novel and suggest that extracellular factors from breast carcinoma play an apoptosis inducing and growth inhibitory role upon on HeLa cells. This study can also support the concept of cancer cachexia and a possible hypothesis for rare chance of synchronous two or more primary tumor in a single patient.

Novel organotin(IV) complexes derived from 4-carboxybenzenesulfonamide: Synthesis, structure and in vitro cytostatic activity evaluation

A new series of 4-carboxybenzenesulfonamide organotin(IV) complexes, [Me3Sn(O2CC6H4-SO2NH2-4)] (1), [n-Bu3Sn(O2CC6H4-SO2NH2-4)] (2), [Ph3Sn(O2CC6H4-SO2NH2-4)] (3), [(Me2Sn)4(μ3-O)2(μ2-OCH3)2(O2CC6H4-SO2NH2-4)2] (4), [(n-Bu2Sn)4(μ3-O)2(μ2-OCH3)2(O2CC6H4-SO2NH2-4)2] (5), [(n-Oct2Sn)4(μ3-O)2(μ2-OCH3)2(O2CC6H4-SO2NH2-4)2] (6), have been designed and synthesized from the reactions of 4-carboxybenzenesulfonamide with the corresponding triorganotin(IV) chloride or diorganotin(IV) oxide. The six complexes were characterized by elemental analysis, FT-IR, NMR (1H, 13C and 119Sn) spectroscopy, as well as by single crystal X-ray diffraction analysis. X-ray diffraction discloses that complexes 1–3 represent mononuclear tin(IV) monomer, and complexes 4–6 adopt tetranuclear tin(IV) ladder-like structure containing two deprotonated ligands linked by three alternate Sn2O2 four-membered rings. Analysis of the non-covalent intermolecular contacts in all complexes reveals the existence of the NH⋯OC, NH⋯OS and Sn⋯O interactions, which play significant function in the supramolecular construction. Furthermore, complexes 1–5 were evaluated for their in vitro cytostatic activity against human cervical carcinoma cell lines (HeLa) and human hepatocellular carcinoma cell lines (HepG-2). The pilot study has confirmed that some of these novel organotin(IV) complexes exhibited high in vitro cytostatic activity.

Naturally Occurring Variations Modulate the Activity of the HPV33 Early Promoter and its Affinity for the E2 Transcription Factor

The human papillomavirus (HPV) Long Control Region (LCR) encompasses the early promoter (EP) that drives transcription of the E6 and E7 oncogenes in keratinocytes and HPV-associated cancers. In this study, the transcriptional activities of the HPV33 EP from the prototype LCR and from eight variants representative of the worldwide diversity of the virus were examined in primary human keratinocytes (PHK) and in the HeLa cervical carcinoma cell line by luciferase reporter-gene assays. Remarkably, the two variations with the greatest effect on the EP in PHK were C7732G and a 79-bp deletion that were associated with high-grade cervical lesions and persistent infections, respectively, in epidemiological studies. In contrast, the three variations most active in HeLa cells were C7537A, A7874C and A7879G. A7874C, which lies within an E2-binding sequence, is also shown to increase the activity and binding of E2 at this site. Collectively, these results indicate that naturally-occurring variations affect the HPV33 EP differentially in PHK than in cancer cells and, furthermore, that they can also alter its regulation by E2. These findings provide a molecular basis for rationalizing the results of previous epidemiological studies and for understanding the contribution of LCR polymorphisms to the oncogenicity and persistence of HPV33 infections.

Synthesis of deuterium-enriched sorafenib derivatives and evaluation of their biological activities.

Deuterium substitution has been widely known that can improve the pharmacokinetic profiles due to isotope effect. Herein, a series of deuterated sorafenib derivatives have been synthesized and characterized by 1H NMR, 13C NMR and MS. Their antitumor activities were evaluated in vitro against human hepatoma cell line HepG2 and human cervical carcinoma cell line HeLa. The LogP values were detected by high-performance liquid chromatography. Subsequently, the metabolic stability and pharmacokinetics study were assessed in vitro and in vivo.

Annexin A5 overexpression might suppress proliferation and metastasis of human uterine cervical carcinoma cells.

Annexin A5 (ANXA5) is a kind of Ca2+-dependent phospholipid binding protein which is involved in cell membrane dynamics and organization. Recent data showed that ANXA5 might involve in tumorigenesis. To explore what role ANXA5 play in human uterine cervical carcinoma. In this study, a recombined ANXA5 plasmid was constructed and uterine cervical carcinoma cell lines HeLa and SiHa were transfected with it. After ANXA5 overexpression was determined by Western Blot, cell proliferation test was detected by MTT assay and colony formation assay respectively. FACS assay and Hochest33258 staining methods were employed to detect cell apoptosis. To further investigate whether ANXA5 influence cell migration and invasion, wound healing assay and transwell assay were applied. At the same time, the relative mechanism was investigated. When ANXA5 expression increased, cell proliferation was inhibited by regulating the expression of bcl-2 and bax while cell metastasis was suppressed by regulating E-cadherin and MMP-9 expression. ANXA5 overexpression in the uterine cervical carcinoma might play important roles in cell proliferation and metastasis of uterine cervical cancer cells and act as an anti-cancer gene in uterine cervical cancer.

2-Substituted-1-(2-morpholinoethyl)-1H-naphtho[2,3-d]imidazole-4,9-diones: Design, synthesis and antiproliferative activity

Thirty-six of novel compounds 2-substituted-1-(2-morpholinoethyl)-1H-naphtho[2,3-d]imidazole-4,9-diones, bearing a N-(2-morpholinoethyl) group and a 2-substituted imidazole segment on a naphthoquinone skeleton, were designed, synthesized and tested as anticancer agents. Cytotoxicity was evaluated in vitro against three human cancer cell lines: human breast carcinoma cell line (MCF-7), human cervical carcinoma cell line (Hela), and human lung carcinoma cell line (A549); and one normal cell line: mouse fibroblast cell line (L929). Among them, the compound 2-(3-chloro-4-methoxyphenyl)-1-(2-morpholinoethyl)-1H-naphtho[2,3-d]imidazole-4,9-dione showed good antiproliferative activity against MCF-7, Hela and A549 (IC50 values are equal to 10.6 μM, 8.3 μM and 4.3 μM respectively) and low cytotoxicity to L929 (IC50 value is equal to 67.3 μM).

Different mitochondrial fragmentation after irradiation with X-rays and carbon ions in HeLa cells and its influence on cellular apoptosis

Although mitochondria are known to play an important role in radiation-induced cellular damage, the mechanisms by which ionizing radiation modulates mitochondrial dynamics are largely unknown. In this study, human cervical carcinoma cell line HeLa was used to demonstrate the different modes of mitochondrial network in response to different quality radiations such as low linear energy transfer (LET) X-rays and high-LET carbon ions. Mitochondria fragmented into punctate and clustered ones upon carbon ion irradiation in a dose- and LET-dependent manner, which was associated with apoptotic cell death. In contrast, low-dose X-ray irradiation promoted mitochondrial fusion while mitochondrial fission was detected until the radiation dose was more than 1 Gy. This fission was driven by ERK1/2-mediated phosphorylation of Drp1 on Serine 616. Inhibition of mitochondrial fragmentation suppressed the radiation-induced apoptosis and thus enhanced the resistance of cells to carbon ions and high-dose X-rays, but not for cells irradiated with X-rays at the low dose. Our results suggest that radiations of different qualities cause diverse changes of mitochondrial dynamics in cancer cells, which play an important role in determining the cell fate.

Inhibition of cell proliferation and migration through nucleobase-modified polyamidoamine-mediated p53 delivery.

IntroductionThe nucleobase 2-amino-6-chloropurine-modified polyamidoamine (AP-PAMAM) was used as a carrier for p53 gene delivery to achieve the antitumor effects.Methods and materialsThe condensation of p53 plasmid was studied through gel retardation assay, and the transfection efficiency was evaluated through the transfection assay of pEGFP-N3 and pGL-3 plasmids. Using human cervical carcinoma cell line HeLa as a model, the inhibition of cell proliferation and migration was studied through flow cytometry, wound healing and Transwell migration assays, respectively. The p53 expression level was detected through quantitative polymerase chain reaction and Western blotting analyses.ResultsThe carrier could condense p53 plasmid into stable nanoparticles at N/P ratios of 2.0, and higher transfection efficiency than polyamidoamine (PAMAM) could be obtained at all the N/P ratios studied. AP-PAMAM-mediated p53 delivery could achieve stronger antiproliferative effect than PAMAM/p53. The antiproliferative effect was identified to be triggered by the induction of cell apoptosis (apoptotic ratio of 26.17%) and cell cycle arrest at S phase. Additionally, AP-PAMAM/p53 transfection has been found to suppress the cell migration and invasion of cancer cells. Finally, the enhanced p53 expression level could be detected after p53 transfection at mRNA and protein levels.ConclusionThe PAMAM derivative-mediated p53 delivery could be a promising strategy for achieving tumor gene therapy.

Implication of KRT16, FAM129A and HKDC1 genes as ATF4 regulated components of the integrated stress response.

The ATF4 transcription factor is a key regulator of the adaptive integrated stress response (ISR) induced by various stresses and pathologies. Identification of novel transcription targets of ATF4 during ISR would contribute to the understanding of adaptive networks and help to identify novel therapeutic targets. We were previously searching for genes that display an inverse regulation mode by the transcription factors ATF4 and p53 in response to mitochondrial respiration chain complex III inhibition. Among the selected candidates the human genes for cytokeratine 16 (KRT16), anti-apoptotic protein Niban (FAM129A) and hexokinase HKDC1 have been found highly responsive to ATF4 overexpression. Here we explored potential roles of the induction of KRT16, FAM129A and HKDC1 genes in ISR. As verified by RT-qPCR, a dysfunction of mitochondrial respiration chain and ER stress resulted in a partially ATF4-dependent stimulation of KRT16, FAM129A and HKDC1 expression in the HCT116 colon carcinoma cell line. ISRIB, a specific inhibitor of ISR, was able to downregulate the ER stress-induced levels of KRT16, FAM129A and HKDC1 transcripts. An inhibition of ATF4 by RNAi attenuated the induction of KRT16, FAM129A and HKDC1 mRNAs in response to ER stress or to a dysfunctional mitochondrial respiration. The similar induction of the three genes was observed in another tumor-derived cervical carcinoma cell line HeLa. However, in HaCaT and HEK293T cells that display transformed phenotypes, but do not originate from patient-derived tumors, the ER stress-inducing treatments resulted in an upregulation of FAM129A and HKDC1, but not KRT16 transcripts, By a luciferase reporter approach we identified a highly active ATF4-responsive element within the upstream region of the KRT16 gene. The results suggest a conditional regulation of KRT16 gene by ATF4 that may be inhibited in normal cells, but engaged during cancer progression. Potential roles of KRT16, FAM129A and HKDC1 genes upregulation in adaptive stress responses and pathologies are discussed.

Two new secondary metabolites from a mangrove-derived fungus Cladosporium sp. JJM22

Two new compounds (1 and 2), together with six known compounds (3–8), were obtained from the Cladosporium sp. JJM22, an endophytic fungus isolated from the stem bark of the mangrove plant Ceriops tagal collected in South China Sea. Their structures were elucidated on the basis of detailed spectroscopic analysis. The absolute configurations of 1 and 2 were confirmed by the comparison of optical rotation and the CD data with those of known compounds. The inhibitory activities of the isolated compounds against six terrestrial pathogenic bacteria and human cervical carcinoma Hela cell line were evaluated. Compound 3 exhibited a broad spectrum of antibacterial activities.

Analysis and evaluation of the antimicrobial and anticancer activities of the essential oil isolated from Foeniculum vulgare from Hamedan, Iran

In this study, biological properties of the essential oil isolated from seeds of Foeniculum vulgare (F. vulgare) were evaluated. GC-MS analysis revealed Trans-Anethole (80.63%), L-Fenchone (11.57%), Estragole (3.67%) and Limonene (2.68%) were the major compounds of the essential oil. Antibacterial activity of the essential oil against nine Gram-positive and Gram-negative strains was studied using disc diffusion and micro-well dilution assays. Essential oil exhibited the antibacterial activity against three Gram-negative strains of Pseudomonas aeruginosa, Escherichia coli, and Shigella dysenteriae. The preliminary study on toxicity of seed oil was performed using Brine Shrimp lethality test (BSLT). Results indicated the high toxicity effect of essential oil (LC50 = 10 μg/mL). In vitro anticancer activity of seed oil was investigated against human breast cancer (MDA-Mb) and cervical epithelioid carcinoma (Hela) cell lines by MTT assay. Results showed the seed oil behave as a very potent anticancer agent with IC50 of lower than 10 μg/mL in both cases.

Synthesis of gold(I) phosphine complexes containing the 2-BrC6F4PPh2 ligand: Evaluation of anticancer activity in 2D and 3D spheroidal models of HeLa cancer cells

Newly synthesised mononuclear gold complexes containing the 2-BrC6F4PPh2 ligand have been fully characterised and their anticancer activity towards five human tumor [prostate (PC3), glioblastoma (U87MG), cervical (HeLa), fibrosarcoma (HT1080), ovarian (SKOV-3)] and normal human embryonic kidney (Hek-293T) cell lines investigated. Some of the synthesised gold complexes displayed higher cytotoxicity than cisplatin towards PC-3, HeLa and U87MG cells and inhibited the thioredoxin reductase (TrxR) enzyme, which is considered a potential target for new compounds in cancer treatment. The more physiologically relevant tumor spheroid assay demonstrated the superior potency of these gold phosphine complexes in inhibiting the growth of cervical carcinoma cell line HeLa (3D) spheroidal models. The mechanism of cell death was shown to be apoptotic cell death through cell cycle arrest, mitochondrial membrane depolarisation and increased ROS production.

Synthesis and evaluation of antitumor activity of new 4-substituted thieno[3,2-d]pyrimidine and thienotriazolopyrimidine derivatives.

3-Methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[3,2-d]pyrimidin- 4(1H)-one (2), on treatment with phosphorous oxychoride, affored 4-chloro-3-methyl-6-phenyl -thieno[3,2-d]pyrimidine- 2(3H)-thione (3). A series of novel 6-phenyl-thieno[3,2-d]pyrimidine derivatives 4-9 bearing different functional groups were synthesized via treatment of compound 3 with different reagents. On the other hand, compound 2 was used to synthesize ethyl-[(3-methyl-6-phenyl-2-thioxo-2,3-dihydrothieno[ 3,2-d]pyrimidin-4-yl)-oxy]acetate (10), 2-hydrazinyl- -3-methyl-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (11), 3-methyl-2-(methyl-sulfanyl)-6-phenyl-thieno[3,2-d]pyrimidin- 4(3H)-one (12) and N-(phenyl)/4-chlorophenyl or methoxy- phenyl)-2-[(3-methyl-4-oxo-6-phenyl-3,4-dihydrothieno[ 3,2-d]pyrimidin-2-yl)-sulfanyl]-acetamide (13a-c). In addition, compound 12 was used to synthesize thieno[1,2,4] triazolopyrimidine derivatives 14 and 15 and 3-methyl-2-(methyl-sulfonyl)-6-phenyl-thieno[3,2-d]pyrimidin-4(3H)-one (16) through the reaction with the respective reagents. Moreover, the reaction of 16 with 4-phenylenediamine gave 2-[(4-aminophenyl)-amino]-3-methyl-6-phenyl-thieno[3,2-d] pyrimidin-4(3H)-one (17), which reacted with methanesulfonyl chloride to afford N-{4-[(3-methyl-4-oxo-6-phenyl-3H,4H- -thieno[3,2-d]pyrimidin-2-yl)-amino]phenyl}-methanesulfonamide (18). The majority of the newly synthesized compounds displayed potent anticancer activity, comparable to that of doxorubicin, on three human cancer cell lines, including the human breast adenocarcinoma cell line (MCF-7), cervical carcinoma cell line (HeLa) and colonic carcinoma cell line (HCT- 116). Compounds 18, 13b and 10 were nearly as active as doxorubicin whereas compounds 6, 7b and 15 exhibited marked growth inhibition, but still lower than doxorubicin.

Effect of Ku80 on the radiosensitization of cisplatin in the cervical carcinoma cell line HeLa.

Cisplatin chemotherapy in combination with radiotherapy is the primary therapeutic strategy for the treatment of cervical cancer; however, the underlying molecular mechanism for cisplatin radiosensitization remains unknown. The aim of the present study was to investigate the effect of Ku80, a DNA double-strand break (DSB) repair protein, on cisplatin radiosensitization in cervical cancer. The pre-established Ku80 suppression cervical cancer cell line HeLa/Ku80-siRNA and the normal HeLa cell line underwent 6 MV X-ray irradiation (6 Gy) individually or in combination with 5 µg/ml cisplatin treatment. Alterations in apoptosis, the cell cycle and γH2AX expression were detected. Following irradiation individually and combined with cisplatin, compared with normal HeLa cells, HeLa/Ku80-siRNAexhibited an increased rate of apoptosis (P<0.05). It was identified that the earlier cisplatin was administered following irradiation, the higher the rate of apoptosis. Cell cycle analysis indicated that, following irradiation combined with cisplatin, the cells were arrested in G1 and S phase rather than in G2/M phase following irradiation alone. Microscopic imaging of immunofluorescence staining and western blotting identified that HeLa/Ku80-siRNA cells exhibited more γH2AX foci remaining following treatment with irradiation and cisplatin, particularly in the group treated with 6 Gy irradiation for 1 h together with 23 h of exposure to cisplatin. Irradiation in combination with cisplatin promoted the apoptosis of HeLa cells in association with the inhibition of Ku80, and it was identified that the earlier cisplatin was administered following irradiation, the more apoptosis was induced. This maybe because irradiation combined with cisplatin is able to arrest cells in G1 and S phase to rapidly repair damaged DNA, and the lack of Ku80 induces the inability to repair DSB, resulting in increased apoptosis. The results of the present study suggest that Ku80 may be a potent molecular target in cisplatin radiosensitization.

Environmentally Responsive Dual-Targeting Nanoparticles: Improving Drug Accumulation in Cancer Cells as a Way of Preventing Anticancer Drug Efflux

Drug targeting and stimuli-responsive drug release are 2 active areas of cancer research and hold tremendous potential in the management of cancer drug resistance. In this study, I addressed this issue and focused on the synthesis and characterization of pH-responsive Fe3O4@SiO2(FITC)-BTN/folic acid/DOX multifunctional nanoparticles aiming to increase drug accumulation in malignancies with both dual active targeting and endosomal drug release properties. Dye-doped silica magnetic-fluorescent composite was constructed by a simple coprecipitation of Fe+2/Fe+3 salts followed by sol-gel formation and dual-targeting function was obtained by conjugating folate and biotin moieties on the silica surface of nanoparticles via an esterification reaction. Doxorubicin was then successfully attached on the amine-functionalized nanoparticles using a pH-sensitive Schiff-base formation. The physicochemical characterization of the structure was performed by dynamic light scattering, zeta potential measurement, X-ray diffraction, Fourier transform infrared spectroscopy, electron microscopy techniques, and an in vitro pH-dependent release study. Cellular uptake and cytotoxicity experiments demonstrated an enhanced intracellular delivery and reduction of cancer cell viability in the cervical carcinoma HeLa cell line. Furthermore, proapoptotic studies showed that the nanoparticles increased the apoptotic rates within the same cancer cells. The preliminary cell tests confirm the potential of these multifunctional nanoparticles against the development of drug resistance in cancer cells.

Targeted delivery of mesoporous silica nanoparticles loaded monastrol into cancer cells: an in vitro study

Monastrol is a simple low molecular weight dihydropyrimidine-based kinesin Eg5 inhibitor. Its low cellular activity and its non-drug-like properties have impeded its further development. In a previous report, we have reported various topological parameters to improve the pharmacokinetic properties of monastrol. The purpose of this study is to determine the loading and release feasibility of poorly water-soluble monastrol into the synthesized mesoporous silica nanoparticles (MSNs). The synthesis of MSNs was attained by the ammonia-catalysed hydrolysis and condensation of TEOS in ethanol using polysorbate-80 as surfactant. These were characterized by BET surface area and pore size distribution analyses, SEM, XRD, UV and FTIR spectroscopy. The synthesized monastrol was successfully loaded on MSNPs and coated by hydrogels for successful controlled drug delivery. In vitro release studies are done by simple dialysis method. Monastrol-loaded MSNPs were tested on human cervical epithelial malignant carcinoma (HeLa) cell lines for studying their anticancer activity. Our presented system described a reliable method for targeted delivery of monastrol into the cancer cells in vitro.

Assessment of free radical scavenging and anti-proliferative activities of Tinospora cordifolia Miers (Willd)

BackgroundTinospora cordifolia (Guduchi or Amrita) is an important drug of Ayurvedic System of Medicine and found mention in various classical texts for the treatment of diseases such as jaundice, fever, diabetes, cancer and skin disease etc. In view of its traditional claims, antioxidant and anti-proliferative activities were evaluated in the present study.MethodsEthanol extract (TCE) and subsequent petroleum ether (TCP), dichloromethane (TCD), n-Butanol (TCB) and aqueous (TCA) fractions of were prepared from stems of T cordifolia. Total phenolic, flavonoid content and anti-oxidant activity was assessed by different methods. Anti-proliferative activity was assessed in cervical carcinoma (HeLa) cell lines by MTT and SRB assay.ResultsEthanol extract and n-butanol fractions shown to be superior in their scavenging activity in all the tested methods. n-butanol fractions shown antioxidant activity with an IC50 of 14.81 ± 0.53, 29.48 ± 2.23, 58.20 ± 0.70 and 21.17 ± 1.19 μg/mL by DPPH, ABTS, Nitric oxide and iron chelating activities respectively. Anti-proliferative activity results demonstrates that the TCD and ethanol extract of T cordifolia exhibits potent cytotoxic effect against HeLa with an IC50 of 54.23 ± 0.94 μg/mL and 101.26 ± 1.42 μg/mL respectively by MTT assay; and with an IC50 of 48.91 ± 0.33 μg/mL and 87.93 ± 0.85 μg/mL respectively by SRB assay.ConclusionThe outcomes of the present study support the fact that T Cordifolia is a promising source of antioxidant agent and propose its further investigation. Moreover, dichloromethane fraction of T cordifolia shown to be the most potent anti-proliferative fraction and further mechanistic and phytochemical investigations are under way to identify the active principles.

Synthesis and in vitro anticancer activity of 23(23′)E-benzylidenespirostanols derived from steroid sapogenins

Benzylidenespirostanols were prepared by two-step synthesis including BF3·Et2O-catalyzed aldol condensation of several acetylated steroid sapogenins with benzaldehyde followed by saponification. The obtained compounds showed moderate cytotoxicity against three cancer cell lines (T-lymphoblastic leukemia cell line CEM, breast carcinoma cell line MCF7 and cervical carcinoma cell line HeLa) and normal human fibroblasts (BJ). The most active of the five tested substances was 3c (lowest IC50 for MCF7 cells 19.9±0.1µM) without any selectivity towards human cancer and normal cells, respectively.

ID1056 Synthesis and biological evaluation of novel curcumin derivative with water-soluble phosphate group as potential antitumor agent

Background: Curcumin (diferuloylmethane) is the main natural active polyphenol from the rhizome of Curcuma longa (turmeric) and in others Curcuma spp. The main pharmacological effects include anti-tumor, anti-inflammatory, anti-oxidation, anti-fungal and anti-bacterial activities. However, the clinical application of curcumin is limited by its main drawbacks such as low solubility, poor bioavailability and rapid excretion from the body. In this study, the chemical modification approach was performed to improve the solubility of curcumin in water, at the same time increase the anti-tumor activity.&#x0D; Methods: The water-soluble compound (2-(curcumin-O-yl)ethyl dihydrophosphate, LH-42017) was synthesized by two classical reactions: O-alkylation with 2-bromoethanol to obtain mono-O-(2-hydroxyethyl)-curcumin, followed by esterification using phosphoryl chloride in water and pyridine. The chemical structure was confirmed by IR-, NMR-spectroscopies and mass-spectrometry. The anti-tumor activity of LH-42017 was assessed against hepatocellular carcinoma Hep-G2, human breast cancer MCF-7, human leukemia K562 and human cervical carcinoma HeLa cell lines based on the sulforhodamine B (SRB) assay.&#x0D; Results: LH-42017 was successfully synthesized from curcumin by overall yield of 28.43%. IC50 of original curcumin was 63.55, 90.88, 104.99 and 60.24 µM on Hep-G2, MCF-7, K562 and Hela, respectively. IC50 of LH-42017 was 36.82, 51.60, 60.80 and 26.14 µM on Hep-G2, MCF-7, K562 and Hela, respectively.&#x0D; Conclusion: The novel synthesized compound LH-42017 showed the antitumor activity in 1.7-2.3 times better than original curcumin. The water-soluble phosphate group plays an important role in development of natural curcumin as potential antitumor agent.

FOLIC ACID-CONJUGATED DOXORUBICIN-LOADED PHOTOSENSITIZING MANGANESE FERRITE NANOPARTICLES: SYNTHESIS, CHARACTERIZATION AND ANTICANCER ACTIVITY AGAINST HUMAN CERVICAL CARCINOMA CELL LINE (HELA)

Objective: On account of several complications and adverse effects associated with the use of conventional chemotherapeutic regimen, the advanced drug-targeted therapies have gained the remarkable attention of the researchers due to their fabulous pharmaceutical and therapeutic advantages. The present study was designed with the aim to synthesize manganese ferrite nanoparticles (MnFe2O4 NPs) and folic acid-conjugated doxorubicin (DOX)-loaded manganese ferrite bovine serum albumin NPs (FA-BSA-DOX-MnFe2O4 NPs) using desolvation cross-linking method.Methods: Having assessed their physicochemical characteristics, the prepared NPs were evaluated for hem compatibility, photo-mediated cytotoxicity, and anti-cancer potential against human cervical carcinoma cell line (HeLa) using a range of in vitro assays which include hemolysis assay, sulforhodamine B (SRB) and MTT assays.Results: Spectroscopic characterization revealed that MnFe2O4 NPs were spherical with an average size diameter of approx. 15 nm and a band gap of 1.4 eV. Another remarkable feature of FA-BSA-DOX conjugated MnFe2O4 NPs was high entrapment efficiency (approx. 95%). MTT assay demonstrated that MnFe2O4 NPs revealed potential photosensitizing ability upon exposure to sunlight. FA-BSA-DOX conjugated MnFe2O4 NPs showed promising cytotoxicity against human cervical epithelial malignant carcinoma cell line (HeLa). Interestingly, the cytotoxicity of these NPs was gradually increased with time of exposure to sunlight.Conclusion: These findings suggested that FA-BSA-DOX conjugated MnFe2O4NPs exhibit promising photosensitizing and anticancer potential against human cervical carcinoma and thus can be considered as an alternative targeted therapy against human cervical cancer.