scholarly journals Hmox1 Upregulation Is a Mutual Marker in Human Tumor Cells Exposed to Physical Plasma-Derived Oxidants

Antioxidants ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 151 ◽  
Author(s):  
Sander Bekeschus ◽  
Eric Freund ◽  
Kristian Wende ◽  
Rajesh Gandhirajan ◽  
Anke Schmidt

Increasing numbers of cancer deaths worldwide demand for new treatment avenues. Cold physical plasma is a partially ionized gas expelling a variety of reactive oxygen and nitrogen species, which can be harnesses therapeutically. Plasmas and plasma-treated liquids have antitumor properties in vitro and in vivo. Yet, global response signatures to plasma treatment have not yet been identified. To this end, we screened eight human cancer cell lines to investigate effects of low-dose, tumor-static plasma-treated medium (PTM) on cellular activity, immune-modulatory properties, and transcriptional levels of 22 redox-related genes. With PTM, a moderate reduction of metabolic activity and modest modulation of chemokine/cytokine pattern and markers of immunogenic cell death was observed. Strikingly, the Nuclear factor (erythroid-derived 2)-like 2 (nrf2) target heme oxygenase 1 (hmox1) was upregulated in all cell lines 4 h post PTM-treatment. nrf2 was not changed, but its baseline expression inversely and significantly correlated with hmox1 expression after exposure to PTM. Besides awarding hmox1 a central role with plasma-derived oxidants, we present a transcriptional redox map of 22 targets and chemokine/cytokine secretion map of 13 targets across eight different human tumor cell lines of four tumor entities at baseline activity that are useful for future studies in this field.

2019 ◽  
Vol 17 (1) ◽  
pp. 57-67
Author(s):  
Yepeng Luan ◽  
Jinyi Liu ◽  
Jianjun Gao ◽  
Jinhua Wang

Background: Cancer incidence and mortality have been increasing and cancer is still the leading cause of death all over the world. Despite the enormous progress in cancer treatment, many patients died of ineffective chemotherapy and drug resistance. Therefore, the design and development of anti-cancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. Tricyclic heterocycles, such as phenothiazine, are always important sources of scaffolds for anti-cancer drug discovery. Methods: In this work, ten new urea-containing derivatives of phenothiazine coupled with different kinds of amine motifs at the endpoint through a three carbon long spacer were designed and synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR and HRMS. All the synthesized compounds were tested for their antitumor activity in vitro against the proliferation of PC-3 cells, and the compounds with best potency entered further cytotoxicity evaluations against other 22 human tumor cell lines. Mechanism was also studied. Results: From all data, it showed that among all 10 target compounds, TTi-2 showed the best effect in inhibiting the proliferation of 23 human cancer cell lines while TTi-2 without obvious inhibitory effect on normal cell. Furthermore, our results also showed that TTi-2 could inhibit migration, invasion and colony formation of MDA-MB-231 cells. Finally, TTi-2 can induce arrest of cell cycle at G0/G1 phase and cell apoptosis by activating the caspase 3 activity. Conclusion: All these results suggested that TTi-2 might be used as a promising lead compound for anticancer drug development.


2020 ◽  
Author(s):  
Chenyang He ◽  
Guo Yu ◽  
Anil Kumar Mondru ◽  
Tania Chakraborty ◽  
Souvik Roy

Abstract Background: Our recent investigation directed to synthesize and characterize a novel ruthenium– phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, and to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo approach.Methods: Ruthenium–phloretin complex was synthesized and characterized using various spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human cancer cell lines and finally in an in vivo model of DMBA induced mammary carcinogenesis in ratsResults: Our studies confirm that the chelation of the metal and ligand was materialize by the 3-OH and 9-OH functional groups of the ligand and the complex is found crystalline and was capable of intercalating with CT-DNA. The complex was capable of reducing cellular propagation and initiate apoptotic events in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Additionally, ruthenium-phloretin complex could modulate p53 intervene apoptosis in the breast carcinoma, initiated by the intrinsic apoptotic trail facilitated by the Bcl2 and Bax and at the same time down regulating the PI3K/Akt/mTOR pathway coupled with MMP9 regulated tumor invasive pathways.Conclusions: Ruthenium-phloretin chemotherapy could interrupt, revoke or suspend the succession of breast carcinoma by altering intrinsic apoptosis along with the antiangiogenic pathway, hence fulfilling the role of a prospective candidate in cancer chemotherapeutics in the in the near future.


2020 ◽  
Author(s):  
Chenyang He ◽  
Junli Wang ◽  
Tania Chakraborty ◽  
Souvik Roy

Abstract Background: Our recent investigation directed to synthesize and characterize a novel ruthenium– phloretin complex accompanied by the study of antioxidant in addition to DNA binding capabilities, and to determine the chemotherapeutic activity against breast carcinoma in vitro and in vivo approach.Methods: Ruthenium–phloretin complex was synthesized and characterized using various spectroscopic methods. The complex was further investigated to determine its efficacy in both MCF-7 and MDA-MB-231 human cancer cell lines and finally in an in vivo model of DMBA induced mammary carcinogenesis in ratsResults: Our studies confirm that the chelation of the metal and ligand was materialize by the 3-OH and 9-OH functional groups of the ligand and the complex is found crystalline and was capable of intercalating with CT-DNA. The complex was capable of reducing cellular propagation and initiate apoptotic events in MCF-7 and MDA-MB-231 breast carcinoma cell lines. Additionally, ruthenium-phloretin complex could modulate p53 intervene apoptosis in the breast carcinoma, initiated by the intrinsic apoptotic trail facilitated by the Bcl2 and Bax and at the same time down regulating the PI3K/Akt/mTOR pathway coupled with MMP9 regulated tumor invasive pathways.Conclusions: Ruthenium-phloretin chemotherapy could interrupt, revoke or suspend the succession of breast carcinoma by altering intrinsic apoptosis along with the antiangiogenic pathway, hence fulfilling the role of a prospective candidate in cancer chemotherapeutics in the in the near future.


2021 ◽  
Author(s):  
Lukas Clemens Böckelmann ◽  
Theresa Felix ◽  
Simona Calabrò ◽  
Udo Schumacher

Abstract Background YKL-40, also known as non-enzymatic chitinase-3 like-protein-1 (CHI3L1), is a glycoprotein expressed and secreted mainly by inflammatory cells and tumor cells. Accordingly, several studies demonstrated elevated YKL-40 serum levels in cancer patients and found YKL-40 to be correlated with a poor prognosis and disease severity in some tumor entities. YKL-40 was suggested to be involved in angiogenesis and extracellular matrix remodeling. As yet, however, its precise biological function remains elusive. Methods As YKL-40 protein expression has only been investigated in few malignancies, we employed immunohistochemical detection in a large multi-tumor tissue microarray consisting of 2,310 samples from 72 different tumor entities. In addition, YKL-40 protein expression was determined in primary mouse xenograft tumors derived from human cancer cell lines. Results YKL-40 could be detected in almost all cancer entities and was differently expressed depending on tumor stage and subtype (e.g., thyroid cancer, colorectal cancer, gastric cancer and ovarian cancer). While YKL-40 was absent in in vitro grown human cancer cell lines, YKL-40 expression was upregulated in xenograft tumor tissues in vivo. Conclusions These data provide new insights into YKL-40 expression at the protein level in various tumor entities and its regulation in tumor models. Our data suggest that upregulation of YKL-40 expression is a common feature in vivo and is finely regulated by tumor cell-microenvironment interactions.


Oncotarget ◽  
2016 ◽  
Vol 7 (27) ◽  
pp. 41363-41379 ◽  
Author(s):  
Kowthar Y. Salim ◽  
Saman Maleki Vareki ◽  
Wayne R. Danter ◽  
Serban San-Marina ◽  
James Koropatnick

Author(s):  
Zeenat Ayoub ◽  
Sumera Banoo Malik ◽  
Archana Mehta

Adiantum capillus-veneris, commonly known as maidenhair fern belongs to family Pteridaceae, has traditionally been used in various medicinal preparations as demulcent, expectorant, emmenagogue, diuretic etc. in the form of oil, paste, decoction and powder. It has also prominent role in hair growing and has anti-microbial, anti-inflammatory, anti-diabetic, anti-nociceptive and antioxidant properties of therapeutic interest. This study aimed to investigate the in vitro cytotoxic activity of fractions of ethanolic extract isolated from the aerial part of A. capillus-veneris against some human cancer cell lines such as colon (HCT-116), lung (A549), breast (MCF-7) and pancreatic (MIA PaCa-2) and tumor cell proliferation/inhibition was assessed using MTT assay. The in vivo anticancer activity of hexane fraction was also evaluated against murine Ehrlich ascites carcinoma (EAC) model. The results confirmed that all the fractions of ethanolic extract exhibited promising in vitro inhibition of tumor cell proliferation when tested against different human cancer cell lines. Among all, hexane fraction proved to be more effective having IC50 values 21.72, 22.67, 26.25 μg/mL, for HCT- 116, A-549, MCF-7, respectively, but chloroform fraction revealed to be more cytotoxic against Mia-PACA-2 having IC50 value 14.72 μg/mL. Higher cytotoxic activity is found to be associated with lower IC50 values. The findings showed that all five fractions exhibited dose-dependent killing capabilities in various human derived cancer cell lines at 48 h of treatment. Hexane fraction was found to inhibit tumour growth development by 16.95%, 41.12% and 82.07% at 50, 100 and 200 mg/kg body weight, respectively. Additionally, this fraction was predicted to be non-toxic at the tested doses. The findings indicate that A. capillus-veneris herb is an antineoplastic agent and suggest that further studies evaluating the isolation of active antitumor compounds from A. capillus-veneris and their mechanism(s) of action are necessary.


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