scholarly journals Sea Anemone Heteractis crispa Actinoporin Demonstrates In Vitro Anticancer Activities and Prevents HT-29 Colorectal Cancer Cell Migration

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5979
Author(s):  
Aleksandra Kvetkina ◽  
Olesya Malyarenko ◽  
Aleksandra Pavlenko ◽  
Sergey Dyshlovoy ◽  
Gunhild von Amsberg ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Sea Anemone ◽  
Carcinoma Cells ◽  
Cancer Cell Migration ◽  
Anticancer Activities ◽  
Migratory Activity ◽  
Epidermal Growth ◽  
Ht 29 ◽  
Heteractis Crispa

Actinoporins are the most abundant group of sea anemone cytolytic toxins. Their membranolytic activity is of high interest for the development of novel anticancer drugs. However, to date the activity of actinoporins in malignant cells has been poorly studied. Here, we report on recombinant analog of Hct-S3 (rHct-S3), belonging to the combinatory library of Heteractis crispa actinoporins. rHct-S3 exhibited cytotoxic activity against breast MDA-MB-231 (IC50 = 7.3 µM), colorectal HT-29 (IC50 = 6.8 µM), and melanoma SK-MEL-28 (IC50 = 8.3 µM) cancer cells. The actinoporin effectively prevented epidermal growth factor -induced neoplastic transformation of JB6 Cl41 cells by 34% ± 0.2 and decreased colony formation of HT-29 cells by 47% ± 0.9, MDA-MB-231 cells by 37% ± 1.2, and SK-MEL-28 cells by 34% ± 3.6. Moreover, rHct-S3 decreased proliferation and suppressed migration of colorectal carcinoma cells by 31% ± 5.0 and 99% ± 6.4, respectively. The potent anti-migratory activity was proposed to mediate by decreased matrix metalloproteinases-2 and -9 expression. In addition, rHct-S3 induced programmed cell death by cleavage of caspase-3 and poly (ADP-ribose) polymerase, as well as regulation of Bax and Bcl-2. Our results indicate rHct-S3 to be a promising anticancer drug with a high anti-migratory potential.

Dual inhibitors of epidermal growth factor receptor and topoisomerase IIα derived from a quinoline scaffold

RSC Advances ◽  
2016 ◽  
Vol 6 (81) ◽  
pp. 77717-77734 ◽  
Author(s):  
Monika Chauhan ◽  
Gaurav Joshi ◽  
Harveen Kler ◽  
Archana Kashyap ◽  
Suyog M. Amrutkar ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Anticancer Activities ◽  
Topoisomerase Iiα ◽  
Dual Inhibitors ◽  
Epidermal Growth ◽  
Egfr Kinase

Based on the quinazoline bearing EGFR inhibitors, a series of thirty four compounds having a quinoline scaffold were synthesized and evaluated in vitro for EGFR kinase inhibitory and anticancer activities.

Differential effects of epidermal growth factor (EGF) on cell locomotion and cell proliferation in a cloned human embryonal carcinoma-derived cell line in vitro

1986 ◽  
Vol 86 (1) ◽  
pp. 47-55
Author(s):  
W. Engstrom
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Embryonal Carcinoma ◽  
Carcinoma Cells ◽  
Colony Diameter ◽  
Cell Locomotion ◽  
Epidermal Growth

The effects of epidermal growth factor (EGF) on clones from a human embryonal carcinoma-derived cell line (Tera-2) have been studied. Cells were plated at clonal densities, whereafter the effects of serum and EGF on cell locomotion and cell proliferation were examined. The addition of 50 ngEGF ml-1 resulted in increased migration, as judged by increased colony diameter in the presence of EGF. However, the effect of EGF on cell locomotion was rarely accompanied by any effect on cell proliferation. It was concluded that EGF exerts a preferential effect on cell migration in human embryonal carcinoma cells in vitro.

Synthesis of axially disubstituted silicon phthalocyanines and investigation of their in vitro cytotoxic/phototoxic anticancer activities

2020 ◽  
Vol 25 (01) ◽  
pp. 10-18
Author(s):  
Fatma Yurt ◽  
Ece Tugba Saka ◽  
Zekeriya Biyiklioglu ◽  
Ayça Tunçel ◽  
Derya Ozel ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Colon Adenocarcinoma ◽  
Nuclear Imaging ◽  
Fibroblast Cell ◽  
Target Tissue ◽  
Anticancer Activities ◽  
Human Lung Fibroblast ◽  
Ht 29

In this study, two SiPcs have been selected and the photodynamic therapy potentials were evaluated of the Pcs. Synthesis of Axially 2-decyn-1-oxy disubstituted Es-SiPc-2 was newly synthesized by the reaction of SiPcCl2 with 2-decyn-1-ol in the presence of NaH in toluene. Furthermore, their nuclear imaging potentials were evaluated in human colon adenocarcinoma (HT-29) and human lung fibroblast cell (WI-38) cell lines. The uptake results have indicated that Es-SiPc labeled with [Formula: see text]I radionuclide ([Formula: see text]I-Es-SiPc) was approximately 2-fold higher in the HT-29 cell line than the WI-38 cell line. In other words, the target/non-target tissue ratio is defined as two in the HT-29/WI-38 cell lines. Besides, the uptake values of [Formula: see text]I-Es-SiPc were found to be higher than [Formula: see text]I-Es-SiPc-2. [Formula: see text]I-Es-SiPc and [Formula: see text]I-Es-SiPc-2 are promising for imaging or treating colon adenocarcinoma. In vitrophotodynamic therapy (PDT) studies have shown that both compounds are suitable and can be used in this field. Also, Es-SiPc has been shown to have higher phototoxicity than Es-SiPc-2.

Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells

2018 ◽  
Vol 206 (1-2) ◽  
pp. 46-53 ◽  
Author(s):  
Maryam Sadat Tafakh ◽  
Massoud Saidijam ◽  
Tayebeh Ranjbarnejad ◽  
Sara Malih ◽  
Solmaz Mirzamohammadi ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Caspase 3 ◽  
Mrna Level ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Prostaglandin E Synthase ◽  
Cox 2 ◽  
Ht 29 ◽  
Microsomal Prostaglandin E Synthase

Background: A high expression of prostaglandin E2 (PGE2) is found in colorectal cancer. Therefore, blocking of PGE2 generation has been identified as a promising approach for anticancer therapy. Sulforaphane (SFN), an isothiocyanate derived from glucosinolate, is used as the antioxidant and anticancer agents. Methods: HT-29 cells were treated with various concentrations of SFN and compared to untreated cells for the expression of microsomal prostaglandin E synthase-1 (mPGES-1), cyclooxygenase 2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 and MMP-9 at the mRNA level. The PGE2 level was measured by ELISA assay. Apoptosis was evaluated by the proportion of sub-G1 cells. The activity of caspase-3 was determined using an enzymatic assay. HT-29 cell migration was assessed using a scratch test. Results: SFN preconditioning decreased the expression of COX-2, mPGES-1, HIF-1, VEGF, CXCR4, MMP-2, and MMP-9. An apoptotic effect of SFN was preceded by the activation of caspase-3 as well as accumulation of cells in the sub-G1 phase of the cell cycle. SFN decreased PGE2 generation and inhibited the in vitro motility/wound-healing activity of HT-29 cells. Conclusions: SFN anticancer effects are associated with antiproliferative, antiangiogenic, and antimetastatic activities arising from the downregulation of the COX-2/ mPGES-1 axis.

scholarly journals A Tryptophan Metabolite, 8-Hydroxyquinaldic Acid, Exerts Antiproliferative and Anti-Migratory Effects on Colorectal Cancer Cells

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1655 ◽  
Author(s):  
Katarzyna Walczak ◽  
Ewa Langner ◽  
Karolina Szalast ◽  
Anna Makuch-Kocka ◽  
Piotr Pożarowski ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Mitochondrial Activity ◽  
Cell Cycle Regulators ◽  
Migratory Activity ◽  
Colorectal Cancer Cells ◽  
Induced Changes ◽  
Ht 29

8-Hydroxyquinaldic acid, the end-metabolite of tryptophan, is well-known metal chelator; however, its role in humans, especially in cancer promotion and progression, has not been fully revealed. Importantly, 8-hydroxyquinaldic acid is the analog of kynurenic acid with evidenced antiproliferative activity towards various cancer cells. In this study, we revealed that 8-hydroxyquinaldic acid inhibited not only proliferation and mitochondrial activity in colon cancer HT-29 and LS-180 cells, but it also decreased DNA synthesis up to 90.9% for HT-29 cells and 76.1% for LS-180 cells. 8-Hydroxyquinaldic acid induced changes in protein expression of cell cycle regulators (CDK4, CDK6, cyclin D1, cyclin E) and CDKs inhibitors (p21 Waf1/Cip1, p27 Kip1), but the effect was dependent on the tested cell line. Moreover, 8-hydroxyquinaldic acid inhibited migration of colon cancer HT-29 and LS-180 cells and increased the expression of β-catenin and E-cadherin. Importantly, antiproliferative and anti-migratory concentrations of 8-hydroxyquinaldic acid were non-toxic in vitro and in vivo. We reported for the first time antiproliferative and anti-migratory activity of 8-hydroxyquinaldic acid against colon cancer HT-29 and LS-180 cells.

scholarly journals EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells

2007 ◽  
Vol 179 (6) ◽  
pp. 1247-1259 ◽  
Author(s):  
Jacco van Rheenen ◽  
Xiaoyan Song ◽  
Wies van Roosmalen ◽  
Michael Cammer ◽  
Xiaoming Chen ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Carcinoma Cells ◽  
Actin Binding ◽  
Temporal Regulation ◽  
Vitro Binding ◽  
Epidermal Growth ◽  
Membrane Bound ◽  
Regulation Of Actin Cytoskeleton

Lamellipodial protrusion and directional migration of carcinoma cells towards chemoattractants, such as epidermal growth factor (EGF), depend upon the spatial and temporal regulation of actin cytoskeleton by actin-binding proteins (ABPs). It is generally hypothesized that the activity of many ABPs are temporally and spatially regulated by PIP2; however, this is mainly based on in vitro–binding and structural studies, and generally in vivo evidence is lacking. Here, we provide the first in vivo data that directly visualize the spatial and temporal regulation of cofilin by PIP2 in living cells. We show that EGF induces a rapid loss of PIP2 through PLC activity, resulting in a release and activation of a membrane-bound pool of cofilin. Upon release, we find that cofilin binds to and severs F-actin, which is coincident with actin polymerization and lamellipod formation. Moreover, our data provide evidence for how PLC is involved in the formation of protrusions in breast carcinoma cells during chemotaxis and metastasis towards EGF.

scholarly journals Apoptosis Induced by Ziziphora tenuior Essential Oil in Human Colorectal Cancer Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mohammadreza Azimi ◽  
Jalil Mehrzad ◽  
Armita Ahmadi ◽  
Elnaz Ahmadi ◽  
Ali Ghorbani Ranjbary
Keyword(s):  
Colorectal Cancer ◽  
Essential Oil ◽  
Mtt Assay ◽  
Caspase 3 ◽  
Rna Extraction ◽  
Gastrointestinal Diseases ◽  
Control Group ◽  
Gene Expressions ◽  
Ht 29

Ziziphora (Cacotti in Persian) belongs to the Lamiaceae family (mint group) and is vastly found in Iran and Asia. This traditional medicinal plant is normally used as analgesic and for treatment of particular gastrointestinal diseases. Since colorectal cancer is one of the most common causes of death in the world and the second leading cause of cancer death among adults, there is a pressing need to inhibit this malignancy by using methods with minimal side effects. One of these methods is the use of natural resources such as medical plants. This study is aimed at investigating the expression of apoptosis-related genes in the adjacent culture of colorectal cancer epithelial cells (HT-29) with Ziziphora essential oil (ZEO). The essential oil was extracted from Ziziphora leaves, and its compounds were determined and then added to the HT-29 culture medium at different concentrations. After 24 hours, the HT-29 cells were harvested from the medium and cytotoxicity was analyzed by MTT assay. After MTT assay and determination of the percentage of apoptosis by flow cytometry, RNA extraction was performed and the expression levels of Bax, Bcl-2, caspase 3 (C3), and caspase 9 (C9) were analyzed using newly designed primers by reverse transcription (RT) qPCR method and GeniX6 software. Also, specific antibodies were used for western blot analyses of those molecules. GC analysis revealed 42 different compounds in the ZEO, including pulegone (26.65%), menthone (5.74%), thymol (5.51%), and menthol (1.02%). MTT assay showed that the concentration of 200 μg/ml of ZEO had the highest HT-29 cell death during 24 hours. After incubation with the concentration of 50 μg/ml of ZEO for 24 and 48 hours, caspase 3 and 9 gene expressions in the treated group increased compared to those in the control group ( P < 0.001 ), while the Bcl-2 expression decreased. The results showed that having anticancer compounds, ZEO can increase C3 and C9 and decrease Bcl-2 expressions, causing apoptosis in HT-29 cells in vitro. This can lead to the use of ZEO as a factor for colorectal cancer treatment.

scholarly journals Perkembangan Terapi Kanker Terkait Senyawa Terpineol, P53 dan Caspase 3

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Maya E. W. Moningka
Keyword(s):  
Aspartic Acid ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Caspase 3 ◽  
Suppressor Gene ◽  
Acid Protease ◽  
Caspase 8 ◽  
Anticancer Activities ◽  
P53 Expression

Abstract: Recent anticancer drug development aims to molecular aspect with more specific target without harming healthy cells. Natural resources have been providing promising new anticancer drugs. Terpineol, an essential oil, is one of the anti-breast cancer candidates. Terpineol can be made from turpentine, which is non-wood product of pine tree latex. Alpha-terpineol isolated from terpineol has an anticancer potency and has been proven to inhibit the growth and induce cancer cell death in vitro by inhibiting NF-κB. P53 is a tumor suppressor gene which triggers apoptosis when irreparable DNA damage occurs. Activity of p53 can be altered and/or inhibited by mutation and inactivation of other oncogenes. The main mechanism underlying apoptosis is caspase (cysteine aspartic acid protease) activity. One of the caspases responsible for apoptosis is caspase 3. This caspase 3 can be activated by either intrinsic (mitochondrial signaling) or extrinsic (death ligand) mechanism; the latter involves caspase 8 and 9. Activated caspase 3 will execute the apoptosis inside the cells. Cytotoxic activity of α-terpineol and its involvement in apoptosis, p53 expression, and caspase 3 activities in cancer cell cultures are still being investigated to determine their anticancer activities and the possibility of anticancer drug development.Keywords: cancer therapy, terpineol, p53, caspase-3 Abstrak: Pengembangan obat antikanker saat ini lebih ditujukan pada aspek molekuler dengan adanya target terapi yang lebih spesifik sehingga lebih aman untuk sel-sel tubuh yang normal. Dewasa ini, eksplorasi terhadap bahan alam untuk kandidat obat antikanker semakin dilirik. Minyak esensial terpineol merupakan salah satu bahan pada komposisi obat antikanker payudara. Terpineol dapat dibuat dari terpentin yang merupakan hasil hutan non kayu dari pohon pinus, dengan cara mengambil getahnya. Dari terpineol diisolasi senyawa α-terpineol yang berpotensi sebagai antikanker serta telah terbukti dapat menghambat pertumbuhan dan menginduksi kematian sel tumor melalui mekanisme yang melibatkan inhibisi aktivitas NFкB. Gen p53 merupakan gen tumor supresor yang memicu terjadinya suatu kematian sel atau apoptosis bila terdapat kerusakan DNA dalam upayanya untuk mengatur proliferasi sel. Selain karena adanya mutasi gen p53, inaktivasi dapat terjadi oleh overekspresi onkogen yang nantinya berikatan dengan p53 dan menghambat kerja gen tersebut. Mekanisme utama yang juga mendasari terjadinya apoptosis ialah aktivitas cysteine aspartic acid protease (caspase). Salah satu caspase yang berperan dalam menginduksi apoptosis ialah caspase 3. Caspase ini dapat diaktifkan melalui mekanisme intrinsik (jalur mitokondrial) maupun ekstrinsik (death ligand), dengan bantuan caspase 8 dan caspase 9. Bila caspase 3 teraktifkan maka sebagai caspase eksekutor, akan melakukan tugasnya untuk mengapoptosis sel. Kajian aktivitas sitotoksik senyawa α-terpineol terhadap suatu cell line, pengaruh senyawa tersebut terhadap proses apoptosis, ekspresi p53, dan aktivitas caspase 3 pada berbagai macam kanker masih terus diteliti dalam perkembangannya sebagai obat anti kanker.Kata kunci: terapi kanker, terpineol, p53, caspase-3

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