Signal transducer and activator of transcription 3 activation up-regulates interleukin-6 autocrine production: a biochemical and genetic study of established cancer cell lines and clinical isolated human cancer cells

AbstractNon-canonical inflammasome activation that recognizes intracellular lipopolysaccharide (LPS) causes pyroptosis, the inflammatory death of innate immune cells. The role of pyroptosis in innate immune cells is to rapidly eliminate pathogen-infected cells and limit the replication niche in the host body. Whether this rapid cell elimination process of pyroptosis plays a role in elimination of cancer cells is largely unknown. Our earlier study demonstrated that a multi-functional secreted protein, secretoglobin (SCGB) 3A2, chaperones LPS to cytosol, and activates caspase-11 and the non-canonical inflammasome pathway, leading to pyroptosis. Here we show that SCGB3A2 exhibits marked anti-cancer activity against 5 out of 11 of human non-small cell lung cancer cell lines in mouse xenographs, while no effect was observed in 6 of 6 small cell lung cancer cell lines examined. All SCGB3A2-LPS-sensitive cells express syndecan 1 (SDC1), a SCGB3A2 cell surface receptor, and caspase-4 (CASP4), a critical component of the non-canonical inflammasome pathway. Two epithelial-derived colon cancer cell lines expressing SDC1 and CASP4 were also susceptible to SCGB3A2-LPS treatment. TCGA analysis revealed that lung adenocarcinoma patients with higher SCGB3A2 mRNA levels exhibited better survival. These data suggest that SCGB3A2 uses the machinery of pyroptosis for the elimination of human cancer cells via the non-canonical inflammasome pathway, and that SCGB3A2 may serve as a novel therapeutic to treat cancer, perhaps in combination with immuno and/or targeted therapies.

Download Full-text

Antiproliferation effect of sulforaphene isolated from radish (Raphanus sativus L.) seeds on A549 cells

Applied Biological Chemistry ◽

10.1186/s13765-020-00561-7 ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

Sooyeon Lim ◽

Jin-Chul Ahn ◽

Eun Jin Lee ◽

Jongkee Kim

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

A549 Cells ◽

Cancer Cell Lines ◽

Human Cancer Cells ◽

Induced Apoptosis ◽

Ht 29 ◽

A549 Lung

Abstract Sulforaphene (SFE), a major isothiocyanate in radish seeds, is a close chemical relative of sulforaphane (SFA) isolated from broccoli seeds and florets. The anti-proliferative mechanisms of SFA against cancer cells have been well investigated, but little is known about the potential anti-proliferative effects of SFE. In this study, we showed that SFE purified from radish seeds inhibited the growth of six cancer cell lines (A549, CHO, HeLa, Hepa1c1c7, HT-29, and LnCaP), with relative half maximal inhibitory concentration values ranging from 1.37 to 3.31 μg/mL. Among the six cancer cell lines, SFE showed the greatest growth inhibition against A549 lung cancer cells, where it induced apoptosis by changing the levels of poly(ADP-ribose) polymerase and caspase-3, -8, and -9. Our results indicate that SFE from radish seeds may have significant anti-proliferative potency against a broad range of human cancer cells via induction of apoptosis.

Download Full-text

Sulforaphene Isolated from Radish (Raphanus Sativus L.) Seeds Inhibits Growth of Six Cancer Cell Lines and Induces Apoptosis of A549 Cells

10.20944/preprints201807.0060.v1 ◽

2018 ◽

Author(s):

Sooyeon Lim ◽

Jinchul Ahn ◽

Eun Jin Lee ◽

jongkee Kim

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

A549 Cells ◽

Adenosine Diphosphate ◽

Cancer Cell Lines ◽

Human Cancer Cells ◽

Ic50 Values ◽

Induced Apoptosis

Sulforaphene (SFE), a major isothiocyanate in radish seeds, is a close chemical relative of sulforaphane (SFA) isolated from broccoli seeds and florets. The anti-proliferative mechanisms of SFA against cancer cells have been well investigated, but little is known about the potential anti-proliferative effects of SFE. In this study, we showed that SFE purified from radish seeds inhibited the growth of six cancer cell lines (A549, CHO, HeLa, Hepa1c1c7, HT-29, and LnCaP), with relative half maximal inhibitory concentration (IC50) values ranging from 1.37 to 3.31 g/mL. Among the six cancer cell lines evaluated, SFE showed the greatest growth inhibition against A549 lung cancer cells. In A549 cells, SFE induced apoptosis via changes in the levels of poly (adenosine diphosphate ribose) polymerase and caspase-3, -8, and -9. Our results indicate that SFE from radish seeds may have significant anti-proliferative potency against a broad range of human cancer cells via induction of apoptosis.

Download Full-text

Ruthenium(ii) arene complexes containing benzhydrazone ligands: synthesis, structure and antiproliferative activity

Inorganic Chemistry Frontiers ◽

10.1039/c6qi00197a ◽

2016 ◽

Vol 3 (10) ◽

pp. 1245-1255 ◽

Cited By ~ 41

Author(s):

Mohamed Kasim Mohamed Subarkhan ◽

Rengan Ramesh

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Arene Complexes ◽

Human Cancer Cell Lines ◽

Human Cancer Cells

Six new Ru(ii) arene anthracene benzhydrazone complexes have been synthesized and show excellent cytotoxicity against human cancer cell lines. The results of apoptosis assays demonstrated that complexes4and6are able to induce apoptosis in human cancer cells.

Download Full-text

Triterpenoidal and Phenolic Compounds Isolated from the Aerial Parts of Helicteres hirsuta and their Cytotoxicity on Several Cancer Cell Lines

Natural Product Communications ◽

10.1177/1934578x1901400103 ◽

2019 ◽

Vol 14 (1) ◽

pp. 1934578X1901400

Author(s):

Triet Thanh Nguyen ◽

Nadine Kretschmer ◽

Eva-Maria Pferschy-Wenzig ◽

Olaf Kunert ◽

Rudolf Bauer

Keyword(s):

Phenolic Compounds ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Moderate Activity ◽

Human Cancer Cell Lines ◽

Aerial Parts ◽

Helicteres Isora

Helicteres L. is one of the genera of the Sterculiaceae family with several remarkable activities. Previous studies revealed that terpenoids, flavonoids, and lignans are the dominant constituents of Helicteres species. However, information about this genus is scarce and unsystematic. Most of the phytochemical and pharmacological investigations have been mainly reported on Helicteres angustifolia and Helicteres isora, which are commonly used in China and Indonesia, respectively. In the present study, two terpenoids: 3β- O-acetylbetulinic acid (1) and simiarenol (2) together with three phenolic compounds: 4,4'-sulfinylbis(2-( tert-butyl)-5-methylphenol) (3), 7- O-methylisoscutellarein (4), 7,4'-di- O-methylisoscutellarein (5), and a mixture of stigmasterol and β-sitosterol were isolated and structurally elucidated from the aerial parts of Helicteres hirsuta Lour. Compounds 1-5 were tested for cytotoxicity on four human cancer cell lines: leukemia CCRF-CEM, breast MDA-MB-231, colon HCT116 and glioblastoma U251 cancer cells. Among them, compounds 1 and 3 showed moderate activity on CCRF-CEM and HCT116 cancer cells with IC50 values ranging from 14.6 to 31.5 μM (P < 0.05). This is the first time these compounds have been reported from this plant. To the best of our knowledge, compound 3 is novel in nature although it has been chemically synthesized before, and compounds 1, 2, and 4 are new to this plant family (Sterculiaceae).

Download Full-text

An IMDAF approach to annellated 1,4:5,8-diepoxynaphthalenes and their metathesis reaction leading to novel scaffolds displaying an antiproliferative activity toward cancer cells

New Journal of Chemistry ◽

10.1039/d1nj03991a ◽

2021 ◽

Author(s):

Elizaveta A. Kvyatkovskaya ◽

Kseniya K. Borisova ◽

Polina P. Epifanova ◽

Aleksey A. Senin ◽

Victor N. Khrustalev ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Metathesis Reaction ◽

Human Cancer Cell Lines ◽

Antiproliferative Agent

A 3,5a-epoxyfuro[2,3,4-de]isoquinoline scaffold, the product of ROCM of 1,4:5,8-diepoxynaphthalenes, is a promising antiproliferative agent toward breast and prostate human cancer cell lines.

Download Full-text

Cytotoxic and Anti-Plasmodial Activities of Stephania dielsiana Y.C. Wu Extracts and the Isolated Compounds

Molecules ◽

10.3390/molecules25163755 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3755 ◽

Cited By ~ 1

Author(s):

James Knockleby ◽

Bruno Pradines ◽

Mathieu Gendrot ◽

Joel Mosnier ◽

Thanh Tam Nguyen ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Apoptotic Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

M Cell ◽

Traditional Use ◽

Aurora Kinases ◽

Highly Effective

Natural products remain a viable source of novel therapeutics, and as detection and extraction techniques improve, we can identify more molecules from a broader set of plant tissues. The aim of this study was an investigation of the cytotoxic and anti-plasmodial activities of the methanol extract from Stephania dielsiana Y.C. Wu leaves and its isolated compounds. Our study led to the isolation of seven alkaloids, among which oxostephanine (1) is the most active against several cancer cell lines including HeLa, MDA-MB231, MDA-MB-468, MCF-7, and non-cancer cell lines, such as 184B5 and MCF10A, with IC50 values ranging from 1.66 to 4.35 μM. Morever, oxostephanine (1) is on average two-fold more active against cancer cells than stephanine (3), having a similar chemical structure. Cells treated with oxostephanine (1) are arrested at G2/M cell cycle, followed by the formation of aneuploidy and apoptotic cell death. The G2/M arrest appears to be due, at least in part, to the inactivation of Aurora kinases, which is implicated in the onset and progression of many forms of human cancer. An in-silico molecular modeling study suggests that oxostephanine (1) binds to the ATP binding pocket of Aurora kinases to inactivate their activities. Unlike oxostephanine (1), thailandine (2) is highly effective against only the triple-negative MDA-MB-468 breast cancer cells. However, it showed excellent selectivity against the cancer cell line when compared to its effects on non-cancer cells. Furthermore, thailandine (2) showed excellent anti-plasmodial activity against both chloroquine-susceptible 3D7 and chloroquine-resistant W2 Plasmodium falciparum strains. The structure–activity relationship of isolated compound was also discussed in this study. The results of this study support the traditional use of Stephania dielsiana Y.C. Wu and the lead molecules identified can be further optimized for the development of highly effective and safe anti-cancer and anti-plasmodial drugs.

Download Full-text

In vitro photodynamic treatment of cancer cells induced by aza-BODIPYs

Photochemical & Photobiological Sciences ◽

10.1039/d0pp00026d ◽

2020 ◽

Vol 19 (6) ◽

pp. 790-799

Author(s):

Miryam Chiara Malacarne ◽

Stefano Banfi ◽

Enrico Caruso

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Iodine Atom ◽

Human Cancer ◽

Cancer Cell Lines ◽

Human Cancer Cell ◽

Photodynamic Treatment ◽

Human Cancer Cell Lines

Two new aza-BODIPY photosensitizers featuring an iodine atom on each pyrrolic unit of their structure, were synthesized in fairly good yields and tested in vitro on two human cancer cell lines to assess their photodynamic efficacy.

Download Full-text

A combined computational pipeline to detect circular RNAs in human cancer cells under hypoxic stress

Journal of Molecular Cell Biology ◽

10.1093/jmcb/mjz094 ◽

2019 ◽

Vol 11 (10) ◽

pp. 829-844 ◽

Cited By ~ 5

Author(s):

Antonella Di Liddo ◽

Camila de Oliveira Freitas Machado ◽

Sandra Fischer ◽

Stefanie Ebersberger ◽

Andreas W Heumüller ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Cancer Cell Lines ◽

Metabolic Adaptation ◽

Circular Rnas ◽

Hypoxic Stress ◽

Computational Pipeline ◽

Transcriptional Responses

Abstract Hypoxia is associated with several diseases, including cancer. Cells that are deprived of adequate oxygen supply trigger transcriptional and post-transcriptional responses, which control cellular pathways such as angiogenesis, proliferation, and metabolic adaptation. Circular RNAs (circRNAs) are a novel class of mainly non-coding RNAs, which have been implicated in multiple cancers and attract increasing attention as potential biomarkers. Here, we characterize the circRNA signatures of three different cancer cell lines from cervical (HeLa), breast (MCF-7), and lung (A549) cancer under hypoxia. In order to reliably detect circRNAs, we integrate available tools with custom approaches for quantification and statistical analysis. Using this consolidated computational pipeline, we identify ~12000 circRNAs in the three cancer cell lines. Their molecular characteristics point to an involvement of complementary RNA sequences as well as trans-acting factors in circRNA biogenesis, such as the RNA-binding protein HNRNPC. Notably, we detect a number of circRNAs that are more abundant than their linear counterparts. In addition, 64 circRNAs significantly change in abundance upon hypoxia, in most cases in a cell type-specific manner. In summary, we present a comparative circRNA profiling in human cancer cell lines, which promises novel insights into the biogenesis and function of circRNAs under hypoxic stress.

Download Full-text

Clinical significance of ERas oncogene on cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.15083 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 15083-15083

Author(s):

K. Yasuda ◽

M. Yashiro ◽

T. Sawada ◽

M. Ohira ◽

K. Hirakawa

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Human Cancer ◽

Es Cells ◽

Cancer Cell Lines ◽

Colorectal Cancers ◽

Breast Cancers ◽

Cancer Tissues

15083 Background: Embryonic stem (ES) cells are pluripotent cells derived from early mammalian embryos. When ES cells are subcutaneously injected into immunodeficient or isogenic mice, a teratoma is formed within a few weeks. This tumor is composed of all three germ layers in a disorganized fashion. Thus there could be some common molecular mechanisms shared by ES cells and somatic cancer cells. The ERas oncogene is a recently identified gene that supports the tumorigenic growth of ES cells by producing a constitutively active Ras protein. There have been no report about expression of ERas oncogene on cancer cells until now. The aim of this study is to investigate expression and clinical significance of ERas oncogene on cancer cell lines and clinical cancer tissues. Methods: A panel of 35 human cancer cell lines, 5 normal cell lines, and 20 patiants with gastric cancer tissues were used in this study. ERas mRNA expression was examined by reverse transcription-polymerase chain reaction. The effect of the DNA methyl transferase inhibitor, 5-aza-2’- deoxycitydine on the ERas expression was analyzed. Methylation of CpG islands of ERas promoter lesion was investigated using bisulfate-directsequence analysis. Results: Expression of ERas mRNA was not found in any normal cells. In contrast, ERas mRNA was found in 15 of 35 cancer cell lines, including 8 of 15 gastric cancers, 4 of 7 colorectal cancers, 2 of 6 pancreas cancers, 1 of 3 breast cancers and none of esophageal cancers. Eras mRNA was found in all gastric cancer tissues, but not normal tissues. 5-aza-2’-deoxycytidine treatment at 2, 5, and 10μM for 24 h resulted in ERas expression in 10 of 20 cancer cell lines with respect to the silencing of ERas, including 7 of 7 gastric cancers, 1 of 3 colorectal cancers and 2 of 3 breast cancers. Methylation of CpG island were found in the cancer cell lines without ERas expression, but not in these with ERas expression. Conclusions: ERas oncogene is associated with the carcinogenesis pathway in human cancer. Eras might be useful marker for cancer diagnosis. No significant financial relationships to disclose.

Download Full-text