scholarly journals Combined Treatment of Heteronemin and Tetrac Induces Antiproliferation in Oral Cancer Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 348
Author(s):  
Chi-Hung Huang ◽  
Tung-Yung Huang ◽  
Wong-Jin Chang ◽  
Yi-shin Pan ◽  
Hung-Ru Chu ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Combined Treatment ◽  
Single Agent ◽  
Cancer Cell Lines ◽  
Cell Counting ◽  
P53 Expression ◽  
Oral Cancer Cells

Background: Heteronemin, a marine sesterterpenoid-type natural product, possesses an antiproliferative effect in cancer cells. In addition, heteronemin has been shown to inhibit p53 expression. Our laboratory has demonstrated that the thyroid hormone deaminated analogue, tetrac, activates p53 and induces antiproliferation in colorectal cancer. However, such drug mechanisms are still to be studied in oral cancer cells. Methods: We investigated the antiproliferative effects by Cell Counting Kit-8 and flow cytometry. The signal transduction pathway was measured by Western blotting analyses. Quantitative PCR was used to evaluate gene expression regulated by heteronemin, 3,3’,5,5’-tetraiodothyroacetic acid (tetrac), or their combined treatment in oral cancer cells. Results: Heteronemin inhibited not only expression of proliferative genes and Homo Sapiens Thrombospondin 1 (THBS-1) but also cell proliferation in both OEC-M1 and SCC-25 cells. Remarkably, heteronemin increased TGF-β1 expression in SCC-25 cells. Tetrac suppressed expression of THBS-1 but not p53 expression in both cancer cell lines. Furthermore, the synergistic effect of tetrac and heteronemin inhibited ERK1/2 activation and heteronemin also blocked STAT3 signaling. Combined treatment increased p53 protein and p53 activation accumulation although heteronemin inhibited p53 expression in both cancer cell lines. The combined treatment induced antiproliferation synergistically more than a single agent. Conclusions: Both heteronemin and tetrac inhibited ERK1/2 activation and increased p53 phosphorylation. They also inhibited THBS-1 expression. Moreover, tetrac suppressed TGF-β expression combined with heteronemin to further enhance antiproliferation and anti-metastasis in oral cancer cells.

Synthesis of Colloidal Quantum Dots Coated with Mercaptosuccinic Acid for Early Detection and Therapeutics of Oral Cancers

2016 ◽  
Vol 15 (04) ◽  
pp. 1650015 ◽  
Author(s):  
G. Jocelin ◽  
A. Arivarasan ◽  
M. Ganesan ◽  
N. Rajendra Prasad ◽  
G. Sasikala
Keyword(s):  
Quantum Dots ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Mercaptosuccinic Acid ◽  
Oral Cancer Cell ◽  
Cdte Qds ◽  
Oral Cancer Cells

Quantum dots (QDs) are gaining widespread recognition for its luminescence behavior and unique photo physical properties as a bio-marker and inorganic fluorophore. In spite of such rampant advantages, its application is clinically hampered depending on the surface coating decreasing its luminescence efficiency. The present study reports preparation of CdTe QDs capped with biologically active thiol based material, mercaptosuccinic acid (MSA) for diagnosis of oral cancer (KB) cells by acting as a fluorophore marking targeted tumor cells and at the same time exhibiting certain cytotoxic effects. Synthesized MSA coated CdTe QDs is spherical in shape with an average particle size of 3–5[Formula: see text]nm. In vitro, the rapid uptake of MSA CdTe QDs in oral cancer cell lines were assessed through fluorescence microscopy. Further, this study evaluates the therapeutic efficiency of MSA CdTe QDs in human oral cancer cell lines using MTT analysis. MSA CdTe QDs exhibit significant cytotoxicity in oral cancer cells in a dose dependent manner with low IC50 when compared with other raw CdTe QDs. MSA CdTe QDs were also treated with human lymphocytes (normal cells) to assess and compare the toxicity profile of QDs in normal and oral tumors. The results of our present study strengthen our hypothesis of using MSA CdTe QDs as detector for tracking and fluorescence imaging of oral cancer cells and exhibiting sufficient cytotoxicity in them.

scholarly journals Differential Effects of Combined ATR/WEE1 Inhibition in Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3790
Author(s):  
Gro Elise Rødland ◽  
Sissel Hauge ◽  
Grete Hasvold ◽  
Lilli T. E. Bay ◽  
Tine T. H. Raabe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Cancer Treatment ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Combined Treatment ◽  
Cancer Cell Lines ◽  
Variable Extent ◽  
Synergistic Induction

Inhibitors of WEE1 and ATR kinases are considered promising for cancer treatment, either as monotherapy or in combination with chemo- or radiotherapy. Here, we addressed whether simultaneous inhibition of WEE1 and ATR might be advantageous. Effects of the WEE1 inhibitor MK1775 and ATR inhibitor VE822 were investigated in U2OS osteosarcoma cells and in four lung cancer cell lines, H460, A549, H1975, and SW900, with different sensitivities to the WEE1 inhibitor. Despite the differences in cytotoxic effects, the WEE1 inhibitor reduced the inhibitory phosphorylation of CDK, leading to increased CDK activity accompanied by ATR activation in all cell lines. However, combining ATR inhibition with WEE1 inhibition could not fully compensate for cell resistance to the WEE1 inhibitor and reduced cell viability to a variable extent. The decreased cell viability upon the combined treatment correlated with a synergistic induction of DNA damage in S-phase in U2OS cells but not in the lung cancer cells. Moreover, less synergy was found between ATR and WEE1 inhibitors upon co-treatment with radiation, suggesting that single inhibitors may be preferable together with radiotherapy. Altogether, our results support that combining WEE1 and ATR inhibitors may be beneficial for cancer treatment in some cases, but also highlight that the effects vary between cancer cell lines.

scholarly journals Soft Coral-Derived Dihydrosinularin Exhibits Antiproliferative Effects Associated with Apoptosis and DNA Damage in Oral Cancer Cells

2021 ◽  
Vol 14 (10) ◽  
pp. 994
Author(s):  
Kun-Han Yang ◽  
Yu-Sheng Lin ◽  
Sheng-Chieh Wang ◽  
Min-Yu Lee ◽  
Jen-Yang Tang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Growth ◽  
Oral Cancer ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Soft Coral ◽  
Oral Cancer Cells

Dihydrosinularin (DHS) is an analog of soft coral-derived sinularin; however, the anticancer effects and mechanisms of DHS have seldom been reported. This investigation examined the antiproliferation ability and mechanisms of DHS on oral cancer cells. In a cell viability assay, DHS showed growth inhibition against several types of oral cancer cell lines (Ca9-22, SCC-9, OECM-1, CAL 27, OC-2, and HSC-3) with no cytotoxic side effects on non-malignant oral cells (HGF-1). Ca9-22 and SCC-9 cell lines showing high susceptibility to DHS were selected to explore the antiproliferation mechanisms of DHS. DHS also causes apoptosis as detected by annexin V, pancaspase, and caspase 3 activation. DHS induces oxidative stress, leading to the generation of reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) and mitochondrial membrane potential (MitoMP) depletion. DHS also induced DNA damage by probing γH2AX phosphorylation. Pretreatment with the ROS scavenger N-acetylcysteine (NAC) can partly counter these DHS-induced changes. We report that the marine natural product DHS can inhibit the cell growth of oral cancer cells. Exploring the mechanisms of this cancer cell growth inhibition, we demonstrate the prominent role DHS plays in oxidative stress.

scholarly journals Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (17) ◽  
pp. 5345
Author(s):  
Benjawan Wudtiwai ◽  
Anupong Makeudom ◽  
Suttichai Krisanaprakornkit ◽  
Peraphan Pothacharoen ◽  
Prachya Kongtawelert
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Adjunctive Treatment ◽  
Migration And Invasion ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Ifn Γ ◽  
Oral Cancer Cells

Up-regulated expression of programmed death-ligand 1 (PD-L1) by interferon-gamma (IFN-γ) has been associated with promotion of cancer cell survival and tumor cell escape from anti-tumor immunity. Therefore, a blockade of PD-L1 expression can potentially be used as a molecular target for cancer therapy. The aim of this study was to investigate whether suppression of IFN-γ induced PD-L1 expression in two oral cancer cell lines, HN6 and HN15, by hesperidin effectively decreased cell proliferation and migration. Further, our objective was to elucidate the involvement of the signal transducer and activator of transcription 1 (STAT1) and STAT3 in the inhibition of induced PD-L1 expression by hesperidin. Our findings indicate that IFN-γ induced expression of PD-L1 protein in HN6 and HN15 via phosphorylation of STAT1 and STAT3 and that hesperidin significantly reduced that induction through suppression of phosphorylated STAT1 and STAT3 in both cell lines. Moreover, hesperidin also significantly decreased the viability, proliferation, migration, and invasion of both cell lines. In conclusion, hesperidin exerted anticancer effects against oral cancer cells through the suppression of PD-L1 expression via inactivation of the STAT1 and STAT3 signaling molecules. The findings of this study support the use of hesperidin as a potential adjunctive treatment for oral cancer.

scholarly journals Magnolol Triggers Caspase-Mediated Apoptotic Cell Death in Human Oral Cancer Cells through JNK1/2 and p38 Pathways

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1295
Author(s):  
Yi-Tzu Chen ◽  
Chiao-Wen Lin ◽  
Chun-Wen Su ◽  
Wei-En Yang ◽  
Chun-Yi Chuang ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cancer Cell Lines ◽  
Heme Oxygenase 1 ◽  
Western Blot Assay ◽  
Oral Cancer Cell

Magnolol is a natural compound extracted from Chinese herbal medicine and can induce apoptosis in numerous types of cancer cells. However, the molecular mechanisms of magnolol in oral cancer are still unclear. In this study, we investigated the anti-cancer effects and underlying mechanisms of magnolol in human oral cancer cell lines. Our results exhibited that magnolol inhibited the cell proliferation via inducing the sub-G1 phase and cell apoptosis of HSC-3 and SCC-9 cells. The human apoptosis array and Western blot assay showed that magnolol increased the expression of cleaved caspase-3 proteins and heme oxygenase-1 (HO-1). Moreover, we proved that magnolol induces apoptosis in oral cancer cell lines via the c-Jun N-terminal kinase (JNK)1/2 and p38 pathways. Overall, the current study supports the role for magnolol as a therapeutic approach for oral cancer through JNK1/2- and p38-mediated caspase activation.

scholarly journals Combinations of vitamins A, D2 and D3 have synergistic effects in gastric and colon cancer cells

2019 ◽  
Vol 9 (12) ◽  
pp. 749
Author(s):  
Sheila Wicks ◽  
Temitope O Lawal ◽  
Nishikant Raut ◽  
Shitalben Patel ◽  
Gail Mahady
Keyword(s):  
Gastric Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Synergistic Effects ◽  
Cancer Cell Lines ◽  
Gastric Cancer Cells ◽  
P53 Expression ◽  
Colon Cancer Cell Lines

Background: Vitamin D was first hypothesized to play a role in cancer chemoprevention in 1980 when it was observed that there was a higher rate of colon cancer in the Northern USA as compared with populations living in the South.  While cholecalciferol (vitamin D3) has been tested in many cancer cell lines, published results for ergocalciferol (vitamin D2) are lacking for most epithelial cell cancers, and combination studies of both D2 and D3 and vitamin A (retinoic acid) are lacking in general. The goal of the study was to investigate the effects of vitamins D2, D3, and A, and combinations on the growth of all gastric and colon cancer cell lines in vitro.Methods: Cell viability and cytotoxicity were determined using the CellTiter-Glo® 2.0, caspase and cytotoxicity activities were determined with Caspase-Glo® 3/7, Caspase 8, ApoTox-Glo™ Triplex Assay. Autophagy was determined using the CYTO-ID® Autophagy Detection Kit 2.0. Gene expression studies were performed using qPCR.Results: Both vitamin D2 and D3 inhibited the growth of all cell lines tested. The IC50 ranged from 19-56 μM. However, when combined (1:1), the IC50 for the combination of D2 and D3 was significantly reduced to a range of 5-6.0 μM indicating synergism. Vitamin A in the form of all trans-retinoic acid (ATRA) also inhibited the growth of all cell lines tested with an IC50 range of 2.6 to 5.6 μM. When ATRA was combined with D2 and D3, the IC50s were again significantly reduced to 0.65 to 1.4 μM, indicating synergistic effects. In gastric and colon cancer cell lines, the combination induced apoptosis via caspase 3/7 and 8, increased the Bax/Bcl-2 ratio; induced autophagy in SW480 cells, increased p53 expression and inhibited the expression of HDACs.Conclusion: Our data demonstrate that vitamins D2, D3 and ATRA reduce the proliferation of colon and gastric cancer cells by increasing Bax expression and the Bax/Bcl-2 ratio, and by increasing caspase activities in favor of apoptosis. The ATRA+D2+D3 combination had synergistic effects in all cell lines tested. In HCT 116 colon cancer and AGS gastric cancer cells, the combination also inhibited HDAC 1/3 and SIRT1/3 and increased p53 expression. While in SW480 colon cancer cells the combination also induced autophagy.Key words: apoptosis, autophagy cholcalciferol, ergocalciferol, gastric cancer, colon cancer, caspase, HDAC inhibitors, SIRT1, synergism

scholarly journals Oxidative Stress-Dependent Synergistic Antiproliferation, Apoptosis, and DNA Damage of Ultraviolet-C and Coral-Derived Sinularin Combined Treatment for Oral Cancer Cells

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2450
Author(s):  
Sheng-Yao Peng ◽  
Jen-Yang Tang ◽  
Ruei-Nian Li ◽  
Hurng-Wern Huang ◽  
Chang-Yi Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Combined Treatment ◽  
Ultraviolet C ◽  
Oral Cancer Cells ◽  
Stress Dependent ◽  
Oral Cells

Combined treatment is increasingly used to improve cancer therapy. Non-ionizing radiation ultraviolet-C (UVC) and sinularin, a coral Sinularia flexibilis-derived cembranolide, were separately reported to provide an antiproliferation function to some kinds of cancer cells. However, an antiproliferation function using the combined treatment of UVC/sinularin has not been investigated as yet. This study aimed to examine the combined antiproliferation function and explore the combination of UVC/sinularin in oral cancer cells compared to normal oral cells. Regarding cell viability, UVC/sinularin displays the synergistic and selective killing of two oral cancer cell lines, but remains non-effective for normal oral cell lines compared to treatments in terms of MTS and ATP assays. In tests using the flow cytometry, luminescence, and Western blotting methods, UVC/sinularin-treated oral cancer cells exhibited higher reactive oxygen species production, mitochondrial superoxide generation, mitochondrial membrane potential destruction, annexin V, pan-caspase, caspase 3/7, and cleaved-poly (ADP-ribose) polymerase expressions than that in normal oral cells. Accordingly, oxidative stress and apoptosis are highly induced in a combined UVC/sinularin treatment. Moreover, UVC/sinularin treatment provides higher G2/M arrest and γH2AX/8-hydroxyl-2′deoxyguanosine-detected DNA damages in oral cancer cells than in the separate treatments. A pretreatment can revert all of these changes of UVC/sinularin treatment with the antioxidant N-acetylcysteine. Taken together, UVC/sinularin acting upon oral cancer cells exhibits a synergistic and selective antiproliferation ability involving oxidative stress-dependent apoptosis and cellular DNA damage with low toxic side effects on normal oral cells.

Synthesis and Characterization of Quinoline-3-Carboxamide Derivatives as Inhibitors of the ATM Kinase

2020 ◽  
Vol 20 (23) ◽  
pp. 2070-2079
Author(s):  
Srimadhavi Ravi ◽  
Sugata Barui ◽  
Sivapriya Kirubakaran ◽  
Parul Duhan ◽  
Kaushik Bhowmik
Keyword(s):  
Western Blot ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Cancer Cell Lines ◽  
Atm Kinase ◽  
Cytotoxicity Studies

Background: The importance of inhibiting the kinases of the DDR pathway for radiosensitizing cancer cells is well established. Cancer cells exploit these kinases for their survival, which leads to the development of resistance towards DNA damaging therapeutics. Objective: In this article, the focus is on targeting the key mediator of the DDR pathway, the ATM kinase. A new set of quinoline-3-carboxamides, as potential inhibitors of ATM, is reported. Methods: Quinoline-3-carboxamide derivatives were synthesized and cytotoxicity assay was performed to analyze the effect of molecules on different cancer cell lines like HCT116, MDA-MB-468, and MDA-MB-231. Results: Three of the synthesized compounds showed promising cytotoxicity towards a selected set of cancer cell lines. Western Blot analysis was also performed by pre-treating the cells with quercetin, a known ATM upregulator, by causing DNA double-strand breaks. SAR studies suggested the importance of the electron-donating nature of the R group for the molecule to be toxic. Finally, Western-Blot analysis confirmed the down-regulation of ATM in the cells. Additionally, the PTEN negative cell line, MDA-MB-468, was more sensitive towards the compounds in comparison with the PTEN positive cell line, MDA-MB-231. Cytotoxicity studies against 293T cells showed that the compounds were at least three times less toxic when compared with HCT116. Conclusion: In conclusion, these experiments will lay the groundwork for the evolution of potent and selective ATM inhibitors for the radio- and chemo-sensitization of cancer cells.

Design, Synthesis and Biological Evaluation: 5-amino-1H-pyrazole-1- carbonyl derivatives as FGFR Inhibitors

2020 ◽  
Vol 17 (11) ◽  
pp. 1330-1341
Author(s):  
Yan Zhang ◽  
Niefang Yu
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Biological Evaluation ◽  
Human Gastric Cancer ◽  
Design Synthesis ◽  
Carbonyl Derivatives ◽  
Ic50 Values ◽  
Inhibitory Activities

Background: Fibroblast growth factors (FGFs) and their high affinity receptors (FGFRs) play a major role in cell proliferation, differentiation, migration, and apoptosis. Aberrant FGFR signaling pathway might accelerate development in a broad panel of malignant solid tumors. However, the full application of most existing small molecule FGFR inhibitors has become a challenge due to the potential target mutation. Hence, it has attracted a great deal of attention from both academic and industrial fields for hunting for novel FGFR inhibitors with potent inhibitory activities and high selectivity. Objective: Novel 5-amino-1H-pyrazole-1-carbonyl derivatives were designed, synthesized, and evaluated as FGFR inhibitors. Methods: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives were established by a condensation of the suitable formyl acetonitrile derivatives with either hydrazine or hydrazide derivatives in the presence of anhydrous ethanol or toluene. The inhibitory activities of the target compounds were screened against the FGFRs and two representative cancer cell lines. Tests were carried out to observe the inhibition of 8e against FGFR phosphorylation and downstream signal phosphorylation in human gastric cancer cell lines (SNU-16). The molecular docking of all the compounds were performed using Molecular Operating Environment in order to evaluate their binding abilities with the corresponding protein kinase. Results: A series of 5-amino-1H-pyrazole-1-carbonyl derivatives have been designed and synthesized, screened for their inhibitory activities against FGFRs and cancer cell lines. Most of the target compounds showed moderate to good anti-proliferate activities against the tested enzymes and cell lines. The most promising compounds 8e suppressed FGFR1-3 with IC50 values of 56.4, 35.2, 95.5 nM, and potently inhibited the SNU-16 and MCF-7 cancer cells with IC50 values of 0.71 1.26 μM, respectively. And 8e inhibited the growth of cancer cells containing FGFR activated by multiple mechanisms. In addition, the binding interactions were quite similar in the molecular models between generated compounds and Debio-1347 with the FGFR1. Conclusion: According to the experimental findings, 5-amino-1H-pyrazole-1-carbonyl might serve as a promising template of an FGFR inhibitor.

Small Molecular Leads Differentially Active Against HER2 Positive and Triple Negative Breast Cancer Cell Lines

2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cancer Type

Background:Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.Methods:The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.Results:Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.Conclusion:These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.

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