scholarly journals Secondary Metabolites of Saussurea costus Leaf Extract Induce Apoptosis in Breast, Liver, and Colon Cancer Cells by Caspase-3-Dependent Intrinsic Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Ali A. Shati ◽  
Mohammed A. Alkahtani ◽  
Mohamed Y. Alfaifi ◽  
Serag Eldin I. Elbehairi ◽  
Fahmy G. Elsaid ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agent ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Expression Level ◽  
Intrinsic Pathway ◽  
Anticancer Effect

Background. Apoptosis, a major form of programmed cell death, plays a vital role in regulating tissue development and maintenance of homeostasis in eukaryotes. Apoptosis can occur via a death receptor-dependent extrinsic or a mitochondrial-dependent intrinsic pathway and can be induced by various chemotherapeutic agents. In this study, the anticancer activity of Saussurea costus and its mode of intervention in human cancer cells of breast, colon, and liver were investigated. Results. In this study, the bioactives of S. costus leaves were extensively extracted in five solvents of different polarity. The cytotoxicity and anticancer effect of the extracted secondary metabolites were investigated against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines using a Sulphorhodamine B (SRB) assay. Secondary metabolites extracted using hexane, methanol, ethyl acetate, and chloroform had the highest cytotoxicity and thus the greatest anticancer effect on all the cancer cell lines tested (IC50; ranging from 0.25 to 2.5 μg/ml), while butanol was comparatively less active (IC50; ranging from 23.2 to 25.5 μg/ml). Further investigation using DNA flow cytometry and fluorescent microscopy revealed that the extract arrested the cells in the G1 phase of cell cycle and induced apoptosis. Furthermore, the elevated expression level of proapoptotic proteins and decreased expression level of antiapoptotic proteins confirmed that the intrinsic (mitochondrial) pathway was involved in mediating the apoptosis of cancer cells upon treatment with S. costus extract. These results altogether suggest that S. costus could be a potential anticancer agent. Conclusion. These results suggest that the S. costus extract is the potential source of the secondary metabolites that could be used as anticancer agent to treat diverse cancers of breast, colon, and liver.

Effect of p-PAQR3Thr32 on PD-L1 expression and immune evasion in gastric cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15571-e15571
Author(s):  
Zhi-Qiang Ling
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Cancer Cell ◽  
Gastric Cancer Cell ◽  
Cancer Cell Lines ◽  
Expression Level ◽  
Gastric Cancer Cells ◽  
Gastric Cancer Cell Lines

e15571 Background: Therapies targeted to the immune checkpoint mediated by PD-1 and PD-L1 show antitumor activity in some solid tumors. We have now examined PD-L1 expression and its regulation in gastric cancer with p-PAQR3Thr32 protein. Methods: The expression of PD-L1 at the protein and mRNA levels in gastric cancer cell lines was examined by flow cytometry, real-time RT-PCR and western blot analysis, respectively. The expression of PD-L1 and p-PAQR3Thr32 protein in 319 surgically resected gastric cancer specimens was evaluated by immunohistochemical analysis. Results: The PD-L1 expression level was higher in gastric cancer cell lines positive for p-PAQR3Thr32 protein induced by glucose starvation than in those negative for the p-PAQR3Thr32 protein. Forced expression of p-PAQR3Thr32 protein in gastric cancer cells markedly increased PD-L1 expression, whereas endogenous PD-L1 expression in p-PAQR3Thr32 protein positive gastric cancer cells was attenuated by treatment with PAQR3 siRNAs. Furthermore, expression of PD-L1 was downregulated by inhibitors of the IRF1 and STAT1 in IFNs-PDL1 signaling pathway in gastric cancer cells positive for p-PAQR3Thr32 protein. At clinical tissue level, the expression level of PD-L1 was positively associated with the presence of p-PAQR3Thr32 protein in gastric cancer specimens. Moreover, the expression level of p-PAQR3Thr32 protein was negatively correlated with CD3, CD8, GZMA (CD8 T cell secretory factor) and positively correlated with CD68 (macrophage marker). Conclusions: Our findings that p-PAQR3Thr32 protein induced by glucose deficiency upregulate PD-L1 by activating IFNs-PDL1 signaling pathway in gastric cancer reveal a direct link between p-PAQR3Thr32 protein and PD-L1 expression. It is suggested that p-PAQR3Thr32 protein may be involved in tumor immunosuppression by inhibiting the proliferation and activity of CD8 T cells in gastric cancer tissues.

scholarly journals The Design and Anticancer Activity of a Citropin1.1 Hybrid Peptide with Selective Activity Against Highly Invasive Metastatic Cell Lines

2019 ◽  
Vol 10 (4) ◽  
pp. 3544-3553 ◽  
Author(s):  
Ammar Almaaytah ◽  
Mohd Alaraj
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Mammalian Cells ◽  
Anticancer Agent ◽  
Consensus Sequence ◽  
Cancer Cell Lines ◽  
Hybrid Peptide ◽  
Citropin 1.1

Citropin 1.1 is an amphipathic alpha-helical cationic peptide that exhibits potent anticancer activity in vitro. Citropin 1.1 was found to be active against 60 cancer cell lines, and this activity was mainly attributed to its ability to bind and lyse membranes of cancer cells. One of the major drawbacks of developing Citropin 1.1 as an anticancer agent is its lack of apparent selectivity toward cancer cells and its ability to cause significant lysis of normal human erythrocytes and mammalian cells at high concentrations. This low selectivity index places severe restraints on the development of Citropin 1.1 as a novel anticancer agent. In this study, we have designed a Citropin 1.1 analog named Citropin A that retained the biological activity of the parent peptide. Citropin A was fused to an anionic fragment in order to neutralize the positive charge carried on the parent peptide rendering it inactive. The resultant hybrid peptide named Citropin-MMP was designed to contain a Matrix metalloproteinase (MMP) cleavable consensus sequence that would be cleaved to release the active Citropin A once it encounters highly metastatic MMP producing cancer cells. Citropin-MMP was found to be completely inactive against non-MMP producing cancer cells and normal mammalian cells. However, when Citropin-MMP was administered to MMP producing cells, its antiproliferative activity was regained, and the peptide displayed exclusive activity against MMP producing cancer cell lines. The data of our study indicate that this enzyme-based cleavage strategy could prove to be successful for the development of Citropin-MMP as a novel therapeutic agent for the purpose of inhibiting the proliferation and invasion of highly metastatic invasive cancer cells.

scholarly journals Discovery of a new tetramethylpyrazine based chalcone with α, β-Unsaturated ketone moiety as a potential anticancer agent

2020 ◽  
Vol 11 (1) ◽  
pp. 826-829
Author(s):  
Syed Nasir Abbas Bukhari
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Carbonyl Group ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agent ◽  
Cancer Cell Lines ◽  
Unsaturated Ketone ◽  
Pancreatic Cancer Cells ◽  
Different Types

In this study, a new ligustrazine-based chalcone molecule has been synthesized that contains an extra α, β-Unsaturated ketone moiety along with α, the β-Unsaturated carbonyl group of chalone. A new tetramethylpyrazine (TMP) based aldehyde was synthesized to make the TMP (ligustrazine) as part of chalcone and then it was reacted with newly synthesized ketone containing additional α, β-Unsaturated ketone moiety. After characterization, this new compound was evaluated for its effect on different types of cancer cell lines and very promising results were obtained. The growth of these cancer cells was inhibited by newly designed and synthesized compounds, especially for colon and pancreatic cancer cells with IC50 0.04 - 0.05 µM

scholarly journals Calponin 3 Regulates Cell Invasion and Doxorubicin Resistance in Gastric Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Keun-Seok Hong ◽  
Hyemin Kim ◽  
Seon-Hee Kim ◽  
Minju Kim ◽  
Jiyun Yoo
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Actin Binding ◽  
Gastric Cancer Cells ◽  
Doxorubicin Resistance

Calponin 3 (CNN3) is an F-actin-binding protein that regulates actin cytoskeletal rearrangement. However, the role of CNN3 in cancer cell invasion and resistance to chemotherapeutic agents has not yet been investigated. The present study was undertaken to investigate whether CNN3 influences cancer-related phenotypes in gastric cancer. We demonstrate that CNN3 contributes to cell invasion and resistance to doxorubicin in gastric cancer. CNN3 expression was markedly elevated in highly invasive cancer cell lines compared to less invasive or noninvasive cancer cell lines. Depletion of CNN3 protein suppressed the invasive ability of gastric cancer cells. The highly invasive MKN-28 gastric cancer cells were more resistant to doxorubicin than the noninvasive MKN-45 cells; however, knockdown of CNN3 expression in MKN-28 cells resensitized them to doxorubicin treatment. Taken together, our results suggest that CNN3 plays a key role in invasiveness and doxorubicin resistance in gastric cancer cells.

scholarly journals Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5769
Author(s):  
Florence Nwakaego Mbaoji ◽  
Justus Amuche Nweze ◽  
Liyan Yang ◽  
Yangbin Huang ◽  
Shushi Huang ◽  
...  
Keyword(s):  
Natural Products ◽  
Secondary Metabolites ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Anticancer Agents ◽  
Marine Natural Products ◽  
Cancer Cell Line ◽  
Cancer Cell Lines ◽  
Wide Range

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potential of marine natural products or their derivatives that were isolated from January 2019 to March 2020, in cancer cell lines, with a focus on the class and type of isolated compounds, source and location of isolation, cancer cell line type, and potency (IC50 values) of the isolated compounds that could be a guide for drug development.

scholarly journals Potential anti-tumor activity of 13.56 MHz alternating magnetic hyperthermia and chemotherapy on the induction of apoptosis in human colon cancer cell lines HT29 and HCT116 by up-regulation of Bax, cleaved caspase 3&9, and cleaved PARP proteins

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Saba Jahangiri ◽  
Samideh Khoei ◽  
Sepideh Khoee ◽  
Majid Safa ◽  
Sakine Shirvalilou ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Polyethylene Glycol ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Caspase 3 ◽  
Magnetic Hyperthermia ◽  
Cancer Cell Lines ◽  
Superparamagnetic Nanoparticles ◽  
Intrinsic Pathway

Abstract Background The purpose of the present study was to evaluate the efficacy of chemo-magnetic hyperthermia (MH), a combination of alternating magnetic field (AMF) and superparamagnetic nanoparticles (SPIONs) coated with Polyethylene glycol-Poly(butyl acrylate)-Polyethylene glycol (PEG-PBA-PEG) carrying 5-Fluorouracil (5-Fu), at inducing apoptosis in the human cancer cell lines HT29 and HCT116. This process can be mediated by alterations in the expression of apoptotic effector proteins, including Bax, Bcl-2, cleaved caspase 3&9, and cleaved PARP, which are involved in the intrinsic pathway of apoptosis. For this purpose, the cells were cultured as monolayers. Then both cell lines were treated with 5-Fu/magnetic nanoparticles and magnetic hyperthermia. Finally, the effect of treatment on cancer cells was determined by Western blot analysis and flow cytometry. Results Our results showed that combined chemo-magnetic thermotherapy significantly increased the apoptosis in colon cancer cells compared to chemotherapy or hyperthermia alone (P < 0.05). Up-regulation of Bax, cleaved caspase 3&9, and cleaved PARP proteins was indicative of apoptosis induction in cancer cells, which are involved in the intrinsic pathway of apoptosis. Conclusions This study demonstrates that localized hyperthermia was able to significantly trigger the 5-Fu release and inhibit cell viability, which, due to the synchronization of hyperthermia and chemotherapy, exacerbated the damage of cancer cells. Graphical Abstract

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.

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