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1.
The use of arginine deiminase (ADI) for arginine depletion therapy is an attractive anticancer approach. Combination strategies are needed to overcome the resistance of severe types of cancer cells to this monotherapy. In the current study, we report, for the first time, that the antioxidant N-acetylcysteine (NAC), which has been used in therapeutic practices for several decades, is a potent enhancer for targeted therapy that utilizes arginine deiminase. We demonstrated that pegylated arginine deiminase (ADI-PEG 20) induces apoptosis and G0/G1 phase arrest in murine MC38 colorectal cancer cells; ADI-PEG 20 induces Ca2+ overload and decreases the mitochondrial membrane potential in MC38 cells. ADI-PEG 20 induced the most important immunogenic cell death (ICD)-associated feature: cell surface exposure of calreticulin (CRT). The antioxidant NAC enhanced the antitumor activity of ADI-PEG 20 and strengthened its ICD-associated features including the secretion of high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). In addition, these regimens resulted in phagocytosis of treated MC38 cancer cells by bone marrow-derived dendritic cells (BMDCs). In conclusion, we describe, for the first time, that NAC in combination with ADI-PEG 20 not only possesses unique cytotoxic anticancer properties but also triggers the hallmarks of immunogenic cell death. Hence, ADI-PEG 20 in combination with NAC may represent a promising approach to treat ADI-sensitive tumors while preventing relapse and metastasis. 相似文献
2.
Christian Leischner Markus Burkard Anja Michel Susanne Berchtold Heike Niessner Luigi Marongiu Christian Busch Jan Frank Ulrich M. Lauer Sascha Venturelli 《Molecules (Basel, Switzerland)》2021,26(18)
Resveratrol, a natural plant phytoalexin, is produced in response to fungal infection or− UV irradiation. It exists as an isomeric pair with cis- and trans-conformation. Whereas multiple physiological effects of the trans-form, including a pronounced anti-tumoral activity, are nowadays elucidated, much less knowledge exists concerning the cis-isomer. In our work, we analyzed the antiproliferative and cytotoxic properties of cis-resveratrol in four different human tumor entities in direct comparison to trans-resveratrol. We used human cell lines as tumor models for hepatocellular carcinoma (HCC; HepG2, Hep3B), colon carcinoma (HCT-116, HCT-116/p53(−/−)), pancreatic carcinoma (Capan-2, MiaPaCa-2), and renal cell carcinoma (A498, SN12C). Increased cytotoxicity in all investigated tumor cells was observed for the trans-isomer. To verify possible effects of the tumor suppressor p53 on resveratrol-induced cell death, we used wild type and p53-deleted or -mutated cell lines for every tested tumor entity. Applying viability and cytotoxicity assays, we demonstrated a differential, dose-dependent sensitivity towards cis- or trans-resveratrol among the respective tumor types. 相似文献
3.
Marta Karkoszka Jakub Rok Klaudia Banach Justyna Kowalska Zuzanna Rzepka Dorota Wrzeniok 《Molecules (Basel, Switzerland)》2022,27(13)
Meloxicam (MLX), which belongs to the oxicam nonsteroidal anti-inflammatory drug derivatives, is an inhibitor of the cyclooxygenase-2 (COX-2) enzyme. Cutaneous adverse effects caused by interaction between UVA radiation and exogenous factors can manifest as phototoxic reactions. Phototoxicity may be a reason for the accumulation of genetic and molecular changes in long-lived cells with low proliferation potential, leading to tumor development. There are several potentially phototoxic drugs, the active component of which is meloxicam. The research aimed to evaluate the influence of MLX and UVAR on skin cells—fibroblasts and melanocytes homeostasis. The obtained results indicated that co-treatment with MLX and UVAR inhibited skin cell proliferation, proportionally to the drug concentration. The observation was confirmed by cytometric analysis of the cell number and viability. The phototoxic effect of MLX was revealed in morphological changes. It was stated that MLX with UVAR lowered the mitochondrial transmembrane potential and changed the cell cycle profile. Additionally, MLX and UVAR caused the disruption of redox homeostasis by lowering the intracellular level of reduced thiols. The presented study revealed that the phototoxic activity of MLX is associated with oxidative stress induction and disruptions in cell homeostasis. The differences in the phototoxic effects of MLX at the cellular level may be related to the different content of melanin pigments. 相似文献
4.
Isabel Canga Pedro Vita Ana Isabel Oliveira María ngeles Castro Cludia Pinho 《Molecules (Basel, Switzerland)》2022,27(15)
In African countries, cancer not only is a growing problem, but also a challenge because available funding and resources are limited. Therefore, African medicinal plants play a significant role in folk medicine and some of them are traditionally used for the treatment of cancer. The high mortality rate and adverse effects associated with cancer treatments have encouraged the search for novel plant-based drugs, thus, some African plants have been studied in recent years as a source of molecules with proven cytotoxicity. This review aims to discuss the cytotoxic activity, in vitro, of African plant crude extracts against cancer cell lines. For the period covered by this review (2017–2021) twenty-three articles were found and analyzed, which included a total of 105 plants, where the main cell lines used were those of breast cancer (MCF-7 and MDA-MBA-231) and colorectal cancer (HCT-116 and Caco-2), which are among the most prevalent cancers in Africa. In these studies, the plant crude extracts were obtained using different solvents, such as ethanol, methanol, or water, with variable results and IC50 values ranging from <20 µg/mL to >200 µg/mL. Water is the preferred solvent for most healers in African countries, however, in some studies, the aqueous extracts were the least potent. Apoptosis and the induction of cell cycle arrest may explain the cytotoxic activity seen in many of the plant extracts studied. Considering that the criteria of cytotoxicity activity for the crude extracts, as established by the American National Cancer Institute (NCI), is an IC50 < 30 μg/mL, we conclude that many extracts from the African flora could be a promising source of cytotoxic agents. 相似文献
5.
An optical biosensor with a stirred cuvette has been used to monitor the interaction between immobilized human serum albumin (HSA) and three water-soluble cationic porphyrins. The binding constants at 25℃ obtained from biosensor analysis were compared with those from fluorescence spectroscopy. The interactions were further investigated at temperatures from 15℃ to 30℃. The thermodynamics parameters, changes of free energy (△G), enthalpy (△H) and entropy (△S), were evaluated from equilibrium data. It appeared that the binding process was governed primarily by electrostatic forces. 相似文献
6.
Nurhanan Murni Yunos Nor Datiakma Mat Amin Muhammad Haffiz Jauri Sui Kiong Ling Nor Hasnida Hassan Nor Jannah Sallehudin 《Molecules (Basel, Switzerland)》2022,27(3)
An alkaloid compound from the hairy root culture of Eurycoma longifolia has been isolated and characterised as 9-methoxycanthin-6-one. The aims of these studies were to investigate the in vitro anti-cancer activities of 9-methoxycanthin-6-one against ovarian cancer (A2780, SKOV-3), breast cancer (MCF-7), colorectal cancer (HT29), skin cancer (A375) and cervical cancer (HeLa) cell lines by using a Sulphorhodamine B assay, and to evaluate the mechanisms of action of 9-methoxycanthin-6-one via the Hoechst 33342 assay and proteomics approach. The results had shown that 9-methoxycanthin-6-one gave IC50 values of 4.04 ± 0.36 µM, 5.80 ± 0.40 µM, 15.09 ± 0.99 µM, 3.79 ± 0.069 µM, 5.71 ± 0.20 µM and 4.30 ± 0.27 µM when tested in A2780, SKOV-3, MCF-7, HT-29, A375 and HeLa cell lines, respectively. It was found that 9-methoxycanthin-6-one induced apoptosis in a concentration dependent manner when analysed via the Hoechst 33342 assay. 9-methoxycanthine-6-one were found to affect the expressions of apoptotic-related proteins, that were proteins pyruvate kinase (PKM), annexin A2 (ANXA2), galectin 3 (LGAL3), heterogeneous nuclear ribonucleoprotein A1 (HNRNP1A1), peroxiredoxin 3 (PRDX3), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the differential analysis of 2-DE profiles between treated and non-treated 9-methoxycanthine-6-one. Proteins such as acetyl-CoA acyltransferase 2 (ACAA2), aldehyde dehydrogenase 1 (ALDH1A1), capping protein (CAPG), eukaryotic translation elongation factor 1 (EEF1A1), malate dehydrogenase 2 (MDH2), purine nucleoside phosphorylase (PNP), and triosephosphate isomerase 1 (TPI1) were also identified to be associated with A2780 cell death induced by 9-methoxycanthine-6-one. These findings may provide a new insight on the mechanisms of action of 9-methoxycanthin-6-one in exerting its anti-cancer effects in vitro. 相似文献
7.
Maria Cristina Marcucci Carlos Rocha Oliveira Daniel Spindola Alyne A. Antunes Leila Y. K. Santana Victor Cavalaro Isabelle B. Costa Ana C. de Carvalho Thiago A. M. Veiga Livia S. Medeiros Lucas dos Santos Zamarioli Carolina P. Gonalves Milena F. Santos Simone S. Grecco Vanessa Y. Suzuki Lydia Masako Ferreira Daniel M. Garcia 《Molecules (Basel, Switzerland)》2022,27(17)
The aim of this study was to investigate the cytotoxic activity of the Coriandrum sativum (C. sativum) ethanolic extract (CSEE) in neuroblastoma cells, chemically characterize the compounds present in the CSEE, and predict the molecular interactions and properties of ADME. Thus, after obtaining the CSEE and performing its chemical characterization through dereplication methods using UPLC/DAD-ESI/HRMS/MS, PM6 methods and the SwissADME drug design platform were used in order to predict molecular interactions and ADME properties. The CSEE was tested for 24 h in neuroblastoma cells to the establishment of the IC50 dose. Then, the cell death was evaluated, using annexin-PI, as well as the activity of the effector caspase 3, and the protein and mRNA levels of Bax and Bcl-2 were analyzed by ELISA and RT-PCR, respectively. By UHPLC/DAD/HRMS-MS/MS analysis, the CSEE showed a high content of isocoumarins-dihydrocoriandrin, coriandrin, and coriandrones A and B, as well as nitrogenated compounds (adenine, adenosine, and tryptophan). Flavonoids (apigenin, hyperoside, and rutin), phospholipids (PAF C-16 and LysoPC (16:0)), and acylglicerol were also identified in lower amount as important compounds with antioxidant activity. The in silico approach results showed that the compounds 1 to 6, which are found mostly in the C. sativum extract, obey the “Five Rules” of Lipinski, suggesting a good pharmacokinetic activity of these compounds when administered orally. The IC50 dose of CSEE (20 µg/mL) inhibited cell proliferation and promoted cell death by the accumulation of cleaved caspase-3 and the externalization of phosphatidylserine. Furthermore, CSEE decreased Bcl-2 and increased Bax, both protein and mRNA levels, suggesting an apoptotic mechanism. CSEE presents cytotoxic effects, promoting cell death. In addition to the promising results predicted through the in silico approach for all compounds, the compound 6 showed the best results in relation to stability due to its GAP value. 相似文献
8.
Hui Li Wei Guo Xiao-jing Ma Jia-shan Li Xin Song 《Applied biochemistry and biotechnology》2017,181(4):1372-1387
Six characteristic di-acetylated lactonic sophorolipids with C16:1, C16:0, C18:0, C18:1, C18:2, and C18:3 fatty acid were obtained from Starmerella bombicola CGMCC 1576. In order to confirm their anticancer activity against human cervical cancer cells and reveal the structure-activity relationships, their anti-proliferation effects on HeLa and CaSki cells were estimated. The cytotoxicity of sophorolipid molecules with different degrees of unsaturation was proved to be influenced by carbon chain length of sophorolipids. The longer the carbon chain length, the stronger the cytotoxicity of sophorolipids. The inhibitory mechanism of a di-acetylated lactonic C18:1 sophorolipid on HeLa cells was investigated. The cells developed many features of apoptosis and cell cycle was blocked at G0 phase and partly at G2 phase. The expression of CHOP and Bip/GRP78 was induced. Caspase-12 and caspase-3 were both activated. However, mitochondrial membrane potential and concentration of cytosolic cytochrome C did not change. The induced apoptosis of HeLa cells was probably triggered through endoplasmic reticulum signaling pathway without involvement of mitochondria. In vivo, 5, 50, and 500 mg/kg lactonic sophorolipids showed 29.90, 41.24, and 52.06 % of inhibition without significant toxicity to tumor-bearing mice, respectively. Our findings may suggest a potential use of sophorolipids in human cervical cancer treatment. 相似文献
9.
10.
S. C. Ng Peter G. Parsons K. Y. Sim Carolyn J. Tranter Rodney H. White David J. Young 《应用有机金属化学》1997,11(7):577-581
Six dibutyl-1,3,2-dioxastannolanes, including two enantiomeric pairs, exhibited greater in vitro antitumour activity towards a variety of human tumour cell lines than cisplatin but with little discrimination, suggesting hydrolysis to a common cytotoxic intermediate. A cell line hypersensitive to mitochondrial inhibitors (CI80–13S) was not sensitive to any of the test compounds, suggesting that cell mechanisms other than, or in addition to, mitochondrial function are targeted by tin antitumour agents. A pigmented melanoma cell line (MM418c5) was resistant to the test compounds, which were found to be sequestered by melanin. This resistance was not observed with triphenyltin hydroxide. © 1997 John Wiley & Sons, Ltd. 相似文献
11.
Nurul Fattin Che Rahim Yazmin Hussin Muhammad Nazirul Mubin Aziz Nurul Elyani Mohamad Swee Keong Yeap Mas Jaffri Masarudin Rasedee Abdullah Muhammad Nadeem Akhtar Noorjahan Banu Alitheen 《Molecules (Basel, Switzerland)》2021,26(5)
Colorectal cancer (CRC) is the third most common type of cancer worldwide and a leading cause of cancer death. According to the Malaysian National Cancer Registry Report 2012–2016, colorectal cancer was the second most common cancer in Malaysia after breast cancer. Recent treatments for colon cancer cases have caused side effects and recurrence in patients. One of the alternative ways to fight cancer is by using natural products. Curcumin is a compound of the rhizomes of Curcuma longa that possesses a broad range of pharmacological activities. Curcumin has been studied for decades but due to its low bioavailability, its usage as a therapeutic agent has been compromised. This has led to the development of a chemically synthesized curcuminoid analogue, (2E,6E)-2,6-bis(2,3-dimethoxybenzylidine) cyclohexanone (DMCH), to overcome the drawbacks. This study aims to examine the potential of DMCH for cytotoxicity, apoptosis induction, and activation of apoptosis-related proteins on the colon cancer cell lines HT29 and SW620. The cytotoxic activity of DMCH was evaluated using the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) cell viability assay on both of the cell lines, HT29 and SW620. To determine the mode of cell death, an acridine orange/propidium iodide (AO/PI) assay was conducted, followed by Annexin V/FITC, cell cycle analysis, and JC-1 assay using a flow cytometer. A proteome profiler angiogenesis assay was conducted to determine the protein expression. The inhibitory concentration (IC50) of DMCH in SW620 and HT29 was 7.50 ± 1.19 and 9.80 ± 0.55 µg/mL, respectively. The treated cells displayed morphological features characteristic of apoptosis. The flow cytometry analysis confirmed that DMCH induced apoptosis as shown by an increase in the sub-G0/G1 population and an increase in the early apoptosis and late apoptosis populations compared with untreated cells. A higher number of apoptotic cells were observed on treated SW620 cells as compared to HT29 cells. Human apoptosis proteome profiler analysis revealed upregulation of Bax and Bad proteins and downregulation of Livin proteins in both the HT29 and SW620 cell lines. Collectively, DMCH induced cell death via apoptosis, and the effect was more pronounced on SW620 metastatic colon cancer cells, suggesting its potential effects as an antimetastatic agent targeting colon cancer cells. 相似文献
12.
Cheng-Zhu Wu Mei-Jia Gao Jie Chen Xiao-Long Sun Ke-Yi Zhang Yi-Qun Dai Tao Ma Hong-Mei Li Yu-Xin Zhang 《Molecules (Basel, Switzerland)》2022,27(20)
Standardized treatment guidelines and effective drugs are not available for human triple-negative breast cancer (TNBC). Many efforts have recently been exerted to investigate the efficacy of natural compounds as anticancer agents owing to their low toxicity. However, no study has examined the effects of isobavachalcone (IBC) on the programmed cell death (PCD) of human triple-negative breast MDA-MB-231 cancer cells. In this study, IBC substantially inhibited the proliferation of MDA-MB-231 cells in concentration- and time-dependent manners. In addition, we found that IBC induced multiple cell death processes, such as apoptosis, necroptosis, and autophagy in MDA-MB-231 cells. The initial mechanism of IBC-mediated cell death in MDA-MB-231 cells involves the downregulation of Akt and p-Akt-473, an increase in the Bax/Bcl-2 ratio, and cleaved caspases-3 induced apoptosis; the upregulation of RIP3, p-RIP3 and MLKL induced necroptosis; as well as a simultaneous increase in LC3-II/I ratio induced autophagy. In addition, we observed that IBC induced mitochondrial dysfunction, thereby decreasing cellular ATP levels and increasing reactive oxygen species accumulation to induce PCD. These results suggest that IBC is a promising lead compound with anti-TNBC activity. 相似文献
13.
Heba A. El Gizawy Alaadin E. El-Haddad Yasmin M. Attia Sally A. Fahim Mai M. Zafer Amr M. Saadeldeen 《Molecules (Basel, Switzerland)》2022,27(8)
Reusing food waste is becoming popular in pharmaceutical industries. Watermelon (Citrullus lanatus) rind is commonly discarded as a major solid waste. Here, the in vitro cytotoxic potential of watermelon rind extracts was screened against a panel of human cancer cell lines. Cell cycle analysis was used to determine the induction of cell death, whereas annexin V-FITC binding, caspase-3, BAX, and BCL-2 mRNA expression levels were used to determine the degree of apoptosis. VEGF-promoting angiogenesis and cell migration were also evaluated. Moreover, the identification of phytoconstituents in the rind extract was achieved using UPLC/T-TOF-MS/MS, and a total of 45 bioactive compounds were detected, including phenolic acids, flavonoids aglycones, and their glycoside derivatives. The tested watermelon rind extracts suppressed cell proliferation in seven cancer cell lines in a concentration-dependent manner. The cytotoxicity of the rind aqueous extract (RAE) was higher compared with that of the other extracts. In addition to a substantial inhibitory effect on cell migration, the RAE triggered apoptosis in HCT116 and Hep2 cells by driving the accumulation of cells in the S phase and elevating the activity of caspase-3 and the BAX/BCL-2 ratio. Thus, a complete phytochemical and cytotoxic investigation of the Citrullus lanatus rind extract may identify its potential potency as an anticancer agent. 相似文献
14.
Cancer is one of the most lethal diseases in the world, and the development and improvement of treatments used in cancer therapies are extremely important for a better quality of life for patients. In view of the current problems in drug administration such as low solubility and adverse effects, the activity of a solid lipid nanoparticle containing docetaxel (SLN-DTX), a drug already used in conventional therapies, was evaluated in a cell line (MDA-MB-231) of one of the most aggressive types of breast cancer with the worst prognosis, triple-negative breast cancer. Viability tests indicated that SLN-DTX has a greater dependence on the treatment dose when compared to the free drug, which indicates a more controlled release of the drug, and both reduced viability by around 50% at a concentration of 1 µg/mL after 72 h. Transmission electron microscopy (TEM) and confocal and light microscopy analyses indicated that after treatment the cells enter a mitotic catastrophe, characteristic of antimitotic drugs that usually make cells progress to death or senescence. Cells treated with both DTX and SLN-DTX showed significant inhibition of mobility, 73.6% and 66.5% when treated with SLN-DTX and DTX, respectively, compared to the 11.4% of the control after 72 h, characteristics that are very relevant in tumor development and progression. SLN-DTX demonstrated its great potential as a nanocarrier by maintaining and improving the drug’s action in the MDA-MB-231 cell line. 相似文献
15.
Francesca Truzzi Anne Whittaker Eros DAmen Camilla Tibaldi Antonella Abate Maria Chiara Valerii Enzo Spisni Giovanni Dinelli 《Molecules (Basel, Switzerland)》2022,27(11)
Impaired autophagy, responsible for increased inflammation, constitutes a risk factor for the more severe COVID-19 outcomes. Spermidine (SPD) is a known autophagy modulator and supplementation for COVID-19 risk groups (including the elderly) is recommended. However, information on the modulatory effects of eugenol (EUG) is scarce. Therefore, the effects of SPD and EUG, both singularly and in combination, on autophagy were investigated using different cell lines (HBEpiC, SHSY5Y, HUVEC, Caco-2, L929 and U937). SPD (0.3 mM), EUG (0.2 mM) and 0.3 mM SPD + 0.2 mM EUG, significantly increased autophagy using the hallmark measure of LC3-II protein accumulation in the cell lines without cytotoxic effects. Using Caco-2 cells as a model, several crucial autophagy proteins were upregulated at all stages of autophagic flux in response to the treatments. This effect was verified by the activation/differentiation and migration of U937 monocytes in a three-dimensional reconstituted intestinal model (Caco-2, L929 and U937 cells). Comparable benefits of SPD, EUG and SPD + EUG in inducing autophagy were shown by the protection of Caco-2 and L929 cells against lipopolysaccharide-induced inflammation. SPD + EUG is an innovative dual therapy capable of stimulating autophagy and reducing inflammation in vitro and could show promise for COVID-19 risk groups. 相似文献
16.
A concise synthesis of pyrano[3,2‐e]indole alkaloid fontanesine B by a Fischer indolization is described. This key Fischer indolization starts with the pyran‐ring and alkene intact, facilitating potential synthetic applications. Furthermore, fontanesine B and its isomer were evaluated for in vitro antiproliferative activity against human colorectal cancer cells. The isomer of fontanesine B showed higher antiproliferative activity than the natural product, fontanesine B ( 2 ). 相似文献
17.
《Analytical letters》2012,45(7):1083-1097
Abstract A sensitive sandwich enzyme immunoassay for human inter-leukin-2 (hIL-2) using monoclonal antibody IS described. A monoclonai anti-hIL-2 IgG-coated poiystyrene ball was incubated with hIL-2 and subsequently with affinity-purified rabbit anti-hIL-2 Fab'-horseradish peroxidase conjugate. Peroxidase activity bound to the polystyrene ball was assayed by fluorimetry using 3-(4-hydroxyphenyl)propionic acid as a substrate. There was no cross-reaction with interleukins 1α and 1bT, epidermal growth factor, insulin and other protein hormones. The detection limit of hIL-2 was 3 pg/tube or 30 ng/1 using 0.1 ml of cuiture supernatant. When peripheral blood mononuclear cells from healthy subjects aged 22-62 yr were cultured in the absence and presence of phytohemagglutinin P for 48 h, hIL-2 levels in the culture supernatants were <0.03-0.10 μg/1 and 0.18-3.7 μg/1, respectively. 相似文献
18.
间氯苯基锰卟啉-5-氟尿嘧啶配合物的合成及其对癌细胞的抑制活性 总被引:1,自引:1,他引:0
合成了4种新5-氟尿嘧啶-卟啉衍生物:5-[3-(2-(5-氟尿嘧啶-1-基)乙氧基)苯基]-10,15,20-三(3-氯苯基)卟啉(1a)、5-[3-(2-(5-氟尿嘧啶-1-基)乙氧基)苯基]- 10,15,20-三(3-氯苯基)锰卟啉(2a)、5-[3-(3-(5-氟尿嘧啶-1-基)丙氧基)苯基]-10,15,20-三(3-氯苯基)锰卟啉(2b)和5-[3-(4-(5-氟尿嘧啶-1-基)丁氧基)苯基]-10,15,20-三(3-氯苯基)锰卟啉(2c),通过UV-Vis、IR、MS及元素分析表征了它们的结构。 用噻唑蓝法(MTT法)测定了化合物2a、2b和2c对人胃癌细胞株BGC-823的抑制活性。 化合物2b的半数抑制浓度IC50为1.34 μmol/L,表明有一定的细胞毒作用。 相似文献
19.
Valentina Pagliara Marina De Rosa Paola Di Donato Rosarita Nasso Antonio DErrico Francesca Cammarota Annarita Poli Mariorosario Masullo Rosaria Arcone 《Molecules (Basel, Switzerland)》2021,26(23)
Among matrix metalloproteinases (MMPs), MMP-9/2 are key enzymes involved in the proteolysis of extracellular matrices in the inflammatory process and in cancer. Since MMP-9/2 expression levels, activity, and secretion is up-regulated during inflammation in response to pro-inflammatory cytokines, such as interleukin-6 (IL-6), many efforts have been devoted to identifying factors that could inhibit the IL-6-induced MMP-9/2 expression. Up to now, several reports indicated that polyphenols from fruits and vegetables are among the major components of health promotion for their antioxidant properties and also for their anti-inflammatory and anti-cancer agents. Among plant derived polyphenols, lemon (Citrus limon) peel extract (LPE) shows anti-cancer properties in various cancer types. In our previous work, we demonstrated that LPE can reduce IL-6-induced migration/invasiveness and MMP-9/2 up-regulation in some gastric cancer cell lines. This study aims to exploit the anti-cancer properties of LPE using an in vitro system model of inflammation, consisting of IL-6-exposed human primary colon cancer cells. We first analyzed the effect of LPE on IL-6-induced cell migration and invasiveness by wound healing and Boyden chamber assay, respectively. The MMP-2 mRNA expression levels and gelatinolytic activity in the cell culture media were determined by q-PCR analysis and gelatin zymography, respectively, and finally, the effects of LPE on IL-6-induced JAK2/STAT3 signaling pathways have been investigated by Western blotting analysis. Our results show that LPE is able to inhibit the IL-6-dependent cell migration and invasiveness associated with the up-regulation of MMP-2 expression levels and that these effects are correlated to the STAT3 phosphorylation in human primary T88 and T93 colon cancer cells. 相似文献
20.
Faris Alrumaihi Masood Alam Khan Ali Yousif Babiker Mohammed Alsaweed Faizul Azam Khaled S. Allemailem Ahmad A. Almatroudi Syed Rizwan Ahamad Mahdi H. Alsugoor Khloud Nawaf Alharbi Nahlah Makki Almansour Arif Khan 《Molecules (Basel, Switzerland)》2022,27(7)
Garlic’s main bioactive organosulfur component, diallyl trisulfide (DATS), has been widely investigated in cancer models. However, DATS is not suitable for clinical use due to its low solubility. The current study seeks to improve DATS bioavailability and assess its chemopreventive and chemosensitizing properties in an AOM-induced colorectal cancer model. The polyethylene glycol coated Distearoylphosphatidylcholine/Cholesterol (DSPC/Chol) comprising DATS-loaded DATSL and doxorubicin (DOXO)-encapsulated DOXL liposomes was prepared and characterized. The changes in the sensitivity of DATS and DOXO by DATSL and DOXL were evaluated in RKO and HT-29 colon cancer cells. The synergistic effect of DATSL and DOXL was studied by cell proliferation assay in the combinations of IC10, IC25, and IC35 of DATSL with the IC10 of DOXL. AOM, DATSL, and DOXL were administered to different groups of mice for a period of 21 weeks. The data exhibited ~93% and ~46% entrapment efficiency of DATSL and DOXL, respectively. The size of sham liposomes was 110.5 nm, whereas DATSL and DOXL were 135.5 nm and 169 nm, respectively. DATSL and DOXL exhibited significant sensitivity in the cell proliferation experiment, lowering their IC50 doses by more than 8- and 14-fold, respectively. However, the DATSL IC10, IC25, and IC35 showed escalating chemosensitivity, and treated the cells in combination with DOXL IC10. Analysis of histopathological, cancer marker enzymes, and antioxidant enzymes revealed that the high dose of DATSL pretreatment and DOXL chemotherapy is highly effective in inhibiting AOM-induced colon cancer promotion. The combination of DATSL and DOXL indicated promise as a colorectal cancer treatment in this study. Intermolecular interactions of DATS and DOXO against numerous cancer targets by molecular docking indicated MMP-9 as the most favourable target for DATS exhibiting binding energy of −4.6 kcal/mol. So far, this is the first research to demonstrate the chemopreventive as well as chemosensitizing potential of DATSL in an animal model of colorectal cancer. 相似文献