Wpływ ekstraktu z wychmielin (Humulus lupulus L.) na przeżywalność ludzkich nowotworowych i prawidłowych komórek jelita

2018 ◽  
Vol 19 (4) ◽  
Author(s):  
Miłosz Caban ◽  
Katarzyna Chojnacka ◽  
Katarzyna Owczarek ◽  
Jakub Fichna ◽  
Anna Podsędek ◽  
...  

Introduction. The hop (Humulus lupulus L.) is used in the production of beer and is responsible for its taste and specific aroma. The female cones of this plant as well as the spent hops after the hops extraction by supercritical CO2 are the source of the substances with high biological activity. These include phenolic compounds among others: catechin, epicatechin, quercetin, kaempferol having a lot of properties which could be used in the medicine. They also demonstrate anti-proliferative activity which is responsible for the inhibition of the cancer cells growth. Aim. The aim of the present study was to evaluate the effect of spent hops extract on the viability of cancer and normal colon epithelial cells. Materials and methods. Three cell lines were tested: two colon cancer lines (SW-480 and HT-29) and normal epithelial colon (CCD841CoN) cell line. The activity of the spent hops extract was tested on the basis of cell growth by means of the MTT test. The cells were incubated with the tested extract at 37°C with the constant of CO2 content in atmosphere for 24, 48, 72 hours. Results. The results showed that tested extract inhibited the growth of two colon cancer cell lines (SW-480 and HT-29) more than the growth of normal cell line (CCD841CoN). The IC50 value for SW-480 cell line was obtained at the concentration 400 μg/ml after 48-hours incubation, for HT-29 cell line at the concentration 200 μg/ml after 72-hours incubation while for normal epithelial CCD841CoN cell line the IC50 value was not received. Conclusions. The spent hops extract has anti-proliferative activity. The most susceptible to extract was SW-480 cell line. The normal CCD841CoN epithelial cells were the least sensitive to the extract activity.

2020 ◽  
Vol 28 (3) ◽  
pp. 185-190
Author(s):  
Maliheh Astaneh ◽  
Soudeh Ghafouri-Fard ◽  
Zahra Fazeli ◽  
Zahra Taherian-Esfahani ◽  
Sepideh Dashti ◽  
...  

BACKGROUND: Recent studies have highlighted the role of natural elements in reduction of cancer cell growth and apoptosis. Koenimbine, a natural product isolated from Murraya koenigii (L) Spreng is a substance with cytotoxic effects on cancer cells. AIM: The effects of koenimbine on HT-29 and SW48 colon cancer cells were evaluated by MTT and Annexin V assays. Expression levels of Wnt/β-catenin pathway genes were quantified by real time PCR. RESULTS: The IC50 values of koenimbine in HT-29 and SW48 was calculated to be 50 μg/ml based on the results of MTT assay. This value was 75 μg/ml in IEC-18 cells which were used as normal control. Annexin V assays revealed induction of cell apoptosis and necrosis in HT-29 and SW48 cells but not IEG18 cells by koenimbine. Koenimbin treatment resulted in significant down-regulation of CYCLD1 expression in SW48 cell line, but up-regulation of this gene in HT29 cell line. Expression of TBLR1, DKK1, GSK3B and β-catenin was significantly decreased after koenimbin treatment in HT-19 cell line. Moreover, expression of DKK1 and GSK3B was significantly decreased after koenimbin treatment in SW-40 cell line. TCF4 expression was not detected in any of cell lines either before or after treatment with koenimbin. CONCLUSION: The current in vitro study showed the cytotoxic effects of koenimbin on two colon cancer cell lines and the effects of this substance on expression of selected genes from Wnt-β catenin pathway. Future in vivo studies are needed before suggestion of this substance as an anti-cancer drug.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15602-e15602
Author(s):  
Harvey J. Kliman ◽  
Ivy S Ling ◽  
Kristin M Milano

e15602 Background: Serotonin (5-HT) is most often considered a neurotransmitter—but in reality its main function is to promote cell proliferation at the site of wound healing via platelet degranulation. We tested the hypothesis that blocking 5-HT production in cancer cells might lead to their death by exposure to a specific tryptophan hydroxylase (TPH) inhibitor: telotristat ethyl (TE). The advantage of this TPH inhibitor is that it does not cross the blood brain barrier and therefore can be used to treat peripheral cancers without danger of interfering with central nervous system 5-HT production. Methods: Three cancer cell lines were tested: liposarcoma (94T778), colon cancer (HT-29), and cholangiocarcinoma (TFK-1). The cells were grown with 0, 5, 15 and 30 µM TE, plated into four-chambered slides with an initial confluence of at least 30%, and cultured for 24-96 H. At the end of each 24 hour period slides were removed, washed, fixed, and stained with hematoxylin for density assessment. Experiments were performed in triplicate and repeated in at least three separate experiments. Cell confluence was determined under low power microscopic examination. Results: In the absence of TE the three cell lines increased their confluence from approximately 30% to 83±5.8% (94T778), 68±11% (HT-29), and 60±16% (TFK-1) over 96 H. When the 94T778 cells were exposed to increasing concentrations of TE their confluence decreased progressively. At a dose of 30 µM cell confluence at 24 H was 3±0%, at 48 H 0.3±0.6%, at 72 H 0±0%, and at 96 H 0±0%. For the HT-29 cells, cell confluence in the 30 µM TE groups were 12±8%, 3±3%, 7±5% and 2±1% at 24, 48, 72 and 96 H, respectively. For the TFK-1cells, cell confluence in the 30 µM TE groups were 7±3%, 20±14%, 17±14% and 24±16% at 24, 48, 72 and 96 H, respectively. Conclusions: Telotristat ethyl is a potent inhibitor of tumor cell line growth. However, the efficacy of this inhibition varies between cell lines. The liposarcoma cell line was most sensitive to TE, with the cholangiocarcinoma cell line being moderately impacted. The colon cancer cell line was intermediate between these two. The differences in response to TE may be related to the specific expression of TPH in any particular cell line, with cancers that are more dependent on 5-HT production being most impacted by TPH blockade. Just as ER PR positive breast cancers are sensitive to blockade of these receptors, TPH positive cancers may be successfully targeted by specific inhibition of the 5-HT biosynthetic pathway.


2018 ◽  
Vol 25 (12) ◽  
pp. 1915-1922
Author(s):  
Fatima Rizvi ◽  
Syed Mahboob Alam ◽  
Farah Asad ◽  
Hina Shams

Background: Breast cancer is most frequently diagnosed cancer globally but there is not any ideal economical and safer agent that not only decreases the progression but also resolve complexities associated with breast cancer such as inflammatory conditions. There was strong link between inflammation and cancer specially breast cancer. Thus by inhibiting the COX enzyme may inhibit the progression of cancer beside of its role in inflammatory conditions of breast. Study Design: Interventional In Vitro trial. Setting: Department of Pharmacology in alliance with PCMD. Period: The duration of study from April 2016 to February 2017. Methodology: For this purpose we used five cancerous lines MCF-7, MDA-MB-231, MCF-10, HT-29 and Hela cell lines. For demonstrating the cytotoxic effects of Apricoxib we used MTT assay (for all cell Lines) and Trypan blue dye exclusion assay (Primarily for MCF-7 cell lines). For calculation of minimum dose required for exert cytotoxic effects of Apricoxib and its selectivitytowards cancerous cells of breast tissue we calculated its IC50 value and Selectivity Index (SI) by MTT assay. Results: Apricoxib significantly reduce the viability of MCF-7, MDA-MB-231, Hela, HT-29 as assessed by MTT assay in dose dependent manner (χ2 (2) = 26.483, p<0.001), (χ2 (2) = 26.49, p<0.001), (χ2 (2) = 26.062, p<0.001) and (χ2 (2) = 26.062, p<0.001) respectively. However Apricoxib had non-significant effects on % viability of MCF-10 cell line (χ2 (2) = 4.167, p=0.654) as assessed by MTT assay. Furthermore Apricoxib had lowest IC50 value against MCF-7 cell line. Conclusion: This study demonstrated that beside of primarily anti-inflammatory effects Apricoxib have additional benefits in term of exerting the cytotoxic effects (in vitro) on cancerous cell lines as indicated by reducing the % viability and reducing the Absorbance value of test sample as compare to control. This opens the newer path for researcher to evaluate different aspects of Apricoxib in field of chemotherapy.


2020 ◽  
Vol 17 (5) ◽  
pp. 563-573 ◽  
Author(s):  
Chandrakant Dhondiram Pawar ◽  
Dattatraya Navnath Pansare ◽  
Devanand Baburao Shinde

Background: Thiophene ring forms important building block in medicinal chemistry. Literature reveals that thiophene ring in combination with different groups shows different activity. By keeping these things in mind we have designed and synthesized a new series of amide and sulfonamide coupled thiophene. A series of novel substituted 3-sulfamoylbenzo[b]thiophene-4- carboxamide molecules containing sulfonamide and amide group were designed, synthesized and used for anti-proliferative activity study. Methods: The final compounds 16-36 were synthesized by using series of reactions comprising sulfonation, sulfonamide coupling, hydrolysis and peptide coupling. The yields of compounds 16- 36 are in the range of 90-98%. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, 13C NMR, LCMS and the purity was checked through HPLC analysis. The compounds were further tested for their in vitro anticancer activity against a series of cell lines A549, HeLa, MCF-7 and Du-145. Results: The intermediates 8-13, 15 and final compounds 16-36 were synthesized in good yields. The synthesized compounds were further tested for their anticancer activity and most of compounds showed moderate to good anticancer activity against all four cell lines. Conclusion: We have synthesized 21 compounds and were screened for anticancer activity against MCF-7, HeLa, A-549 and Du-145 cancer cell lines. Most of the compounds were active for tested cell lines with IC50 value in the range of 1.81 to 9.73 μM. The compounds 18, 19, 21, 25, 30, 31 and 33 are most active in cell line data with IC50 value in the range of 1.81 to 2.52 μM.


2019 ◽  
Vol 9 (4) ◽  
pp. 341-348 ◽  
Author(s):  
Ibrahim Awad Mohammed ◽  
Muhammad Nadeem Akhtar ◽  
Foo Jhi Biau ◽  
Yin Sim Tor ◽  
Seema Zareen ◽  
...  

<P>Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. </P><P> Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. </P><P> Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. </P><P> Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62&#177;0.61 and 4.44&#177;0.66 &#181;g/mL) and pinostrobin chalcone (2), (IC50 = 20.42&#177;2.23 and 22.51&#177;0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. </P><P> Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.</P>


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A925-A925
Author(s):  
Alessandra Romano ◽  
Nunziatina Parrinello ◽  
Sara Marino ◽  
Enrico La Spina ◽  
Massimo Fantini ◽  
...  

BackgroundNEO-201 is an IgG1 mAb targeting variants of CEACAM5/6 and has demonstrated tumor sensitivity and specificity in epithelial cells. Functional analysis has revealed that NEO-201 can engage innate immune effector mechanisms including ADCC and CDC to directly kill tumor cells expressing its target. A recent Phase 1 clinical trial at the NCI has determined both safety and recommended Phase 2 dosing. We have also seen the expression of the NEO-201 target on hematologic cells, specifically Tregs and neutrophils. Due to epitope being expressed both on malignant epithelial cells as well as several hematologic cells, we designed this study to explore the reactivity of NEO-201 against hematological neoplastic cells in vitro.MethodsPhenotypic analysis was conducted by flow cytometry. Cell lines used were six AML (HL60, U937, MOLM13, AML2, IMS-M2 and OCL-AML3), two multiple myelomas (MM) (OPM2, MM1.S), two acute lymphoblastic leukemia (ALL) (SUP-B15, RPMI8402) and four mantle cell lymphoma (MCL) (Jeko-1, Z138, JVM2 and JVM13). Markers used for flow cytometry analysis were CD15, CD45, CD38, CD138, CD14, CD19 and NEO-201. Functional analysis was performed by evaluating the ability of NEO-201 to mediate ADCC activity against AML cell lines using human NK cells as effector cells.Results5 of 6 AML cell lines tested bind to NEO-201 and the% of positive cells were 47%, 99.5%,100%,100% and 97.8% for HL60, U937, MOLM13, AML3 and IMS-M2, respectively. The% of positive cells in the two MM cell line were 99% and 18% for OPM2 and MM1.S, respectively. NEO-201 binding was not detected in the two ALL and the four MCL cell lines tested. Functional analysis has demonstrated that NEO-201 can mediate ADCC activity against the AML cell line (HL60) tested.ConclusionsThis study demonstrates that NEO-201 mAb’s target is expressed in most of the AML cell lines tested in vitro. In addition, we have shown it can mediate ADCC activity against HL60 cells (AML). Together, these findings provide a rationale for further investigation of the role of NEO-201 in AML as well as MM, further exploring patient PBMCs and bone marrow samples.


Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1856
Author(s):  
Ana Čipak Gašparović ◽  
Lidija Milković ◽  
Claudia Rodrigues ◽  
Monika Mlinarić ◽  
Graça Soveral

Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells.


2017 ◽  
Vol 70 (1) ◽  
pp. 136-145 ◽  
Author(s):  
Fredrick Onyango Ogutu ◽  
Tai-Hua Mu ◽  
Hongnan Sun ◽  
Miao Zhang
Keyword(s):  

Author(s):  
Sudipta Jena ◽  
Asit Ray ◽  
Ambika Sahoo ◽  
Prabhat Kumar Das ◽  
Pradeep Kumar Kamila ◽  
...  

Background: The essential oils isolated from several medicinal plants are reported to have anticancer activities. Both the essential oil and extracts of many Piper species (Piperaceae) possess potential cytotoxic effect against cancer cell lines and are being used in traditional system of medicine for the treatment of cancer. There is a need to evaluate and validate the anticancer properties of essential oils extracted from other wild species of Piper. Objective: The current research was undertaken to determine the chemical composition and investigate the anti-proliferative activity of wild growing Piper trioicum leaf essential oil. The selected five major constituents were subjected to molecular docking to identify possible modes of binding against serine/threonine-protein kinase (MST3) protein Methods: The essential oil of leaf of P. trioicum was extracted by hydro distillation method and its chemical composition was carried out by GC-FID and GC-MS. The anti-proliferative activity of the essential oil was evaluated by MTT assay against normal (3T3-L1) and various cancer (HCT 116, HT-29, PC-3 and HepG2) cell lines. Molecular docking analysis was performed using AutoDock 4.2 software. The pharmacokinetic and pharmacodynamic properties of the major constituents were determined using absorption, distribution, metabolization, excretion and toxicity (ADMET) analysis. Results: The GC-MS analysis revealed the identification of 45 constituents with δ-cadinene (19.57%), germacrene-D (8.54%), β-caryophyllene (6.84%), 1-epi-cubenol (4.83%) and α-pinene (4.52%) were found to be predominant constituents in the leaf essential oil of P. trioicum. The highest cytotoxicity of essential oil was observed against HT-29 cells (IC50 value of 33.14 µg/ml). 1-epi-cubenol and δ-Cadinene exhibited low binding energy values of -6.25 and -5.92 kcal/mol, respectively. For prediction of in silico pharmacokinetic and druglike properties of the major compounds, ADMET prediction tool was also used, the results of which came within the ideal range. Conclusion: The present findings demonstrated that P. trioicum essential oil possesses significant anti-proliferative activity and could be effective against cancer treatment.


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