scholarly journals α,β-Thujone suppresses human placental choriocarcinoma cells via metabolic disruption

Reproduction ◽  
2020 ◽  
Vol 159 (6) ◽  
pp. 745-756
Author(s):  
Jin-Young Lee ◽  
Hahyun Park ◽  
Whasun Lim ◽  
Gwonhwa Song
Keyword(s):  
Artemisia Absinthium ◽  
Food Ingredient ◽  
Comprehensive Description ◽  
Apoptotic Pathway ◽  
Anti Cancer ◽  
Therapeutic Properties ◽  
Choriocarcinoma Cells ◽  
Energy Deprivation ◽  
Metabolic Disruption ◽  
Mitochondrial Defect

α,β-Thujone is a natural terpenoid found in many medicinal herbs, such as Artemisia absinthium (wormwood), that exhibits antioxidant, anti-diabetic, and anti-tumorigenic effects. α,β-Thujone has numerous functions; it serves as a food ingredient, cosmetic additive, and medicinal remedy. Although the therapeutic properties of α,β-thujone were previously revealed, a comprehensive description of the mechanisms of its anti-cancer potential in choriocarcinoma is yet to be provided. To our knowledge, this study is the first to demonstrate that α,β-thujone attenuates JEG3 and JAR choriocarcinoma cells through a caspase-dependent intrinsic apoptotic pathway. Moreover, α,β-thujone was demonstrated to induce a global mitochondrial defect and ER stress in choriocarcinoma by causing mitochondrial depolarization, calcium overload, and metabolic alterations, thereby leading to energy deprivation, which eventually contributes to the increase in apoptosis of choriocarcinoma cells. Herein, we also revealed the synergistic anti-cancer activity of α,β-thujone via its sensitization effect on paclitaxel in choriocarcinoma cells. Altogether, our findings suggest that α,β-thujone is a novel, natural pharmacological compound that can be used to treat human placental choriocarcinoma.

scholarly journals Cathepsin S Cleaves BAX as a Novel and Therapeutically Important Regulatory Mechanism for Apoptosis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 339
Author(s):  
Surinder M. Soond ◽  
Lyudmila V. Savvateeva ◽  
Vladimir A. Makarov ◽  
Neonila V. Gorokhovets ◽  
Paul A. Townsend ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Regulatory Mechanism ◽  
Renal Clear Cell Carcinoma ◽  
Cathepsin S ◽  
Apoptotic Pathway ◽  
Intact Cells ◽  
Unique Role ◽  
Bax Protein ◽  
Anti Cancer

Certain lysosomal cathepsin proteins have come into focus as being good candidates for therapeutic targeting, based on them being over-expressed in a variety of cancers and based on their regulation of the apoptotic pathway. Here, we report novel findings that highlight the ability of cathepsin S expression to be up-regulated under Paclitaxel-stimulatory conditions in kidney cell lines and it being able to cleave the apoptotic p21 BAX protein in intact cells and in vitro. Consistent with this, we demonstrate that this effect can be abrogated in vitro and in mammalian cells under conditions that utilize dominant-inhibitory cathepsin S expression, cathepsin S expression-knockdown and through the activity of a novel peptide inhibitor, CS-PEP1. Moreover, we report a unique role for cathepsin S in that it can cleave a polyubiquitinated-BAX protein intermediate and is a step that may contribute to down-regulating post-translationally-modified levels of BAX protein. Finally, CS-PEP1 may possess promising activity as a potential anti-cancer therapeutic against chemotherapeutic-resistant Renal Clear Cell Carcinoma kidney cancer cells and for combined uses with therapeutics such as Paclitaxel.

scholarly journals Evaluation of the Anti-Inflammatory and Anti-Oxidative Effects of Therapeutic Human Lactoferrin Fragments

2021 ◽  
Vol 9 ◽  
Author(s):  
Yu Pan ◽  
Zhao Liu ◽  
Yijie Wang ◽  
Linshen Zhang ◽  
Niying Chua ◽  
...  
Keyword(s):  
Cellular Proliferation ◽  
Skin Inflammation ◽  
Medical Regimen ◽  
Anti Cancer ◽  
Colorectal Cancer Cells ◽  
Inflammatory Bowel ◽  
Therapeutic Properties ◽  
Anti Inflammatory ◽  
Oxidative Effects

Chronic inflammation is considered a pressing health issue that needs resolving. Inflammatory disease such as inflammatory bowel disease requires a long-term medical regimen to prevent disease progression. Conventionally, lactoferrin is used to treat mild gastrointestinal tract and skin inflammation. Protease-digested lactoferrin fragments often exhibit improved therapeutic properties compared to full-length lactoferrin (flHLF). However, there are no studies on the use of protease-digested lactoferrin fragments to treat inflammation. Herein, we assess the anti-inflammatory properties of engineered recombinant lactoferrin fragments (rtHLF4, rteHLF1, and rpHLF2) on non-malignant colonic fibroblast cells and colorectal cancer cells. We found that rtHLF4 is 10 times more effective to prevent inflammation compared to flHLF. These results were investigated by looking into the reactive oxygen species (ROS) production, angiogenesis activity, and cellular proliferation of the treated cells. We have demonstrated in this study the anti-inflammatory properties of the flHLF and the various lactoferrin fragments. These results complement the anti-cancer properties of these proteins that were demonstrated in an earlier study.

scholarly journals Synthesis of 3-Trifluoromethyl-5,6-dihydro-[1,2,4]triazolo Pyrazine Derivatives and Their Anti-Cancer Studies

Molbank ◽  
10.3390/m1173 ◽  
2020 ◽  
Vol 2020 (4) ◽  
pp. M1173
Author(s):  
Rajaiah Raveesha ◽  
Malavalli Guruswamy Dileep Kumar ◽  
Salekoppal Boregowda Benaka Prasad
Keyword(s):  
Colon Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Colon Cancer Cell ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Colon Cancer Cell Lines ◽  
Anti Cancer ◽  
Ht 29

The synthesis of a wide variety of 3-trifluoromethyl-5,6-dihydro-[1,2,4]triazolo pyrazine derivatives, by the treatment of 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride with an array of isocyanates in the presence of triethylamine, is reported. All the target compounds were synthesized in excellent yields under mild reaction conditions. The target molecules were effectively screened for their anti-cancer properties and the results are promising. The resultant compounds were assessed for their antiproliferative action against two human colon cancer cell lines (HCT-116 and HT-29 colon cancer cell lines). The IC50 range was estimated at 6.587 to 11.10 µM showing that compound RB7 had remarkable anticancer movement on HT-29. Additionally, it was discovered that RB7 incited the mitochondrial apoptotic pathway by up-regulating Bax and down-regulating Bcl2, eventually leading to the activation of Caspase 3 in HT-29 cells and initiation of cell death via the mitochondrial apoptotic pathway.

Novel titanocene anti-cancer drugs and their effect on apoptosis and the apoptotic pathway in prostate cancer cells

APOPTOSIS ◽  
2006 ◽  
Vol 11 (7) ◽  
pp. 1205-1214 ◽  
Author(s):  
K. O'Connor ◽  
C. Gill ◽  
M. Tacke ◽  
F.-J. K. Rehmann ◽  
K. Strohfeldt ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Cancer Drugs ◽  
Prostate Cancer Cells ◽  
Apoptotic Pathway ◽  
Anti Cancer

scholarly journals Tumor-suppressive function of methiothepin in human placental choriocarcinoma cells

Reproduction ◽  
2020 ◽  
Vol 160 (6) ◽  
pp. 919-929
Author(s):  
Jin-Young Lee ◽  
Whasun Lim ◽  
Gwonhwa Song
Keyword(s):  
Serotonin Receptor ◽  
Molecular Networks ◽  
Transmembrane Region ◽  
Suppressive Function ◽  
Psychotropic Agent ◽  
Anti Cancer ◽  
Choriocarcinoma Cells ◽  
Tumorigenic Activity ◽  
Tumor Suppressive Function ◽  
Serotonin Receptor Antagonist

Placental choriocarcinoma is a malignant trophoblastic tumor associated with placentation. During placentation, complicated molecular networks are mediated by endocrine and paracrine signals. Serotonin neurotransmitters have been identified in the transmembrane region of human placental choriocarcinoma (HPC) cells as tumor promoters; therefore, their antagonists have anti-cancer properties. Although methiothepin, a serotonin receptor antagonist and FDA-approved psychotropic agent, has shown multi-pharmacological functions in various disease models, its anti-tumorigenic activity and mechanisms underlying its action against HPC are unknown. Therefore, we identified the anti-cancer effects of methiothepin in JEG3 and JAR HPC cells. Methiothepin attenuated mitochondrial function and induced endoplasmic reticular stress, reducing oxidative phosphorylation and causing metabolic shifting in HPC cells. Furthermore, methiothepin showed synergistic pharmacological effects with paclitaxel in HPC cells. Our results highlight the robust tumor-suppressive function of methiothepin in HPC. Our findings provide new insights into the repositioning of methiothepin from a psychotropic agent to novel anti-cancer agents, especially against HPC.

scholarly journals Apomorphine induces mitochondrial-dysfunction-dependent apoptosis in choriocarcinoma

Reproduction ◽  
2020 ◽  
Vol 160 (3) ◽  
pp. 367-377
Author(s):  
Jin-Young Lee ◽  
Jiyeon Ham ◽  
Whasun Lim ◽  
Gwonhwa Song
Keyword(s):  
Molecular Mechanisms ◽  
Drug Repositioning ◽  
Synergistic Effects ◽  
Therapeutic Effects ◽  
Antitumor Effects ◽  
Apoptosis Pathway ◽  
Atp Production ◽  
Intrinsic Apoptosis Pathway ◽  
Choriocarcinoma Cells ◽  
Energy Deprivation

Apomorphine is a derivative of morphine that is used for the treatment of Parkinson’s disease because of its effects on the hypothalamus. Therapeutic effects of apomorphine have also been reported for various neurological diseases and cancers. However, the molecular mechanisms of the antitumor effects of apomorphine are not clear, especially with respect to choriocarcinoma. This is the first study to elucidate the anticancer effects of apomorphine on choriocarcinoma. We found that apomorphine suppressed the viability, proliferation, ATP production, and spheroid formation of JEG3 and JAR choriocarcinoma cells. Moreover, apomorphine activated the intrinsic apoptosis pathway by activating caspases and inhibited the production of anti-apoptotic proteins in choriocarcinoma cells. Further, apomorphine caused depolarization of mitochondria, calcium overload, energy deprivation, and endoplasmic reticulum stress in JEG3 and JAR cells. We confirmed synergistic effects of apomorphine with paclitaxel, a traditional chemotherapeutic agent, and propose that apomorphine could be a potential therapeutic agent in choriocarcinoma and an important candidate for drug repositioning that could help overcome resistance to conventional chemotherapy.

scholarly journals Antibacterial activity of selenium nanoparticles synthesized using Maranta arundinaecea root extract

2020 ◽  
Vol 11 (2) ◽  
pp. 2695-2700
Author(s):  
Balamithra S ◽  
Rajeshkumar S ◽  
Anitha Roy ◽  
Lakshmi T
Keyword(s):  
Antibacterial Activity ◽  
Selenium Nanoparticles ◽  
Root Extract ◽  
Apoptotic Pathway ◽  
Cycle Arrest ◽  
Stomach Pain ◽  
Anti Cancer ◽  
Arrow Root ◽  
Cancer Agent ◽  
Pellet Form

Maranta arundinaecea is otherwise known as arrowroot. It promotes weight loss, treats diahorrea and stimulates the immune system. As Arrowroot is rich in starch, it helps in good digestion by mild laxative in regulating the bowel movement. Also it reduces stomach pain and bloating. Selenium is a semi conductor so it is used in making electrical wires. It is used in potent chemotherapy. It is an anti-cancer agent due to its invasion of apoptotic pathway and cell cycle arrest. Usually the arrow root extract is available as powder. The powder is diluted and mixed into sodium selenite solution and this combination is observed for 3 days. After 3 days, it is centrifuged and collected in a pellet form. The lactobacillus and streptococcus mutants are used for culture of organism for 1 day. The extract is tested for for anti-bacterial activity. Result- It shows the sector where it can inhibit in Streptococcus mutans and lactobacillus. Maranta arundinaecea root mediated selenium nanoparticles shows very good antibacterial activity will used in many biomedical applications is future.

scholarly journals Deoxypodophyllotoxin Exerts Anti-Cancer Effects on Colorectal Cancer Cells Through Induction of Apoptosis and Suppression of Tumorigenesis

2019 ◽  
Vol 20 (11) ◽  
pp. 2612 ◽  
Author(s):  
Chathurika D. B. Gamage ◽  
So-Yeon Park ◽  
Yi Yang ◽  
Rui Zhou ◽  
İsa Taş ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Apoptotic Pathway ◽  
Anti Cancer ◽  
Cervical Tumors ◽  
Skin Xenograft

Deoxypodophyllotoxin (DPT) is a cyclolignan compound that exerts anti-cancer effects against various types of cancers. DPT induces apoptosis and inhibits the growth of breast, brain, prostate, gastric, lung, and cervical tumors. In this study, we sought to determine the effect of DPT on cell proliferation, apoptosis, motility, and tumorigenesis of three colorectal cancer (CRC) cell lines: HT29, DLD1, and Caco2. DPT inhibited the proliferation of these cells. Specifically, the compound-induced mitotic arrest in CRC cells by destabilizing microtubules and activating the mitochondrial apoptotic pathway via regulation of B-cell lymphoma 2 (Bcl-2) family proteins (increasing Bcl-2 associated X (BAX) and decreasing B-cell lymphoma-extra-large (Bcl-xL)) ultimately led to caspase-mediated apoptosis. In addition, DPT inhibited tumorigenesis in vitro, and in vivo skin xenograft experiments revealed that DPT significantly decreased tumor size and tumor weight. Taken together, our results suggest DPT to be a potent compound that is suitable for further exploration as a novel chemotherapeutic for human CRC.

scholarly journals Edible Mushrooms as a Natural Source of Food Ingredient/Additive Replacer

Foods ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2687
Author(s):  
Esmeralda Rangel-Vargas ◽  
Jose Antonio Rodriguez ◽  
Rubén Domínguez ◽  
José Manuel Lorenzo ◽  
Maria Elena Sosa ◽  
...  
Keyword(s):  
Bioactive Compounds ◽  
Review Paper ◽  
Antimicrobial Properties ◽  
Edible Mushrooms ◽  
Food Ingredient ◽  
Edible Species ◽  
Commercial Species ◽  
Textural Parameters ◽  
Ancient Times ◽  
Therapeutic Properties

Although mushrooms have been exploited since ancient times because of their particular taste and therapeutic properties, the interest in edible species as a source of ingredients and bioactive compounds is recent. Their valuable nutritional contents in protein, dietary fiber and bioactive compounds make them ideal candidates for use in foods in efforts to improve their nutritional profiles. This trend is in line with the consumer’s growing demand for more plant-based foods. The present review paper explores different studies focused on the use of common edible mushrooms as an ingredient and additive replacer by using them in fresh, dried, or even extract forms, as meat, fat, flour, salt, phosphates, and antioxidant replacers. The replacement of meat, fat, flour, and salt by mushrooms from commercial species has been successful despite sensorial and textural parameters can be affected. Moderate concentrations of mushrooms, especially in powder form, should be considered, particularly in non-familiarized consumers. In the case of antioxidant and antimicrobial properties, results are variable, and more studies are necessary to determine the chemical aspects involved.

scholarly journals Mesenchymal stromal cells as carriers of IL-12 reduce primary and metastatic tumors of murine melanoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Natalia Kułach ◽  
Ewelina Pilny ◽  
Tomasz Cichoń ◽  
Justyna Czapla ◽  
Magdalena Jarosz-Biej ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Vascular Density ◽  
Strong Immune Response ◽  
M1 Macrophages ◽  
Murine Melanoma ◽  
Anti Cancer ◽  
Inhibition Of Tumor Growth ◽  
Therapeutic Properties

AbstractDue to immunosuppressive properties and confirmed tropism towards cancer cells mesenchymal stromal cells (MSC) have been used in many trials. In our study we used these cells as carriers of IL-12 in the treatment of mice with primary and metastatic B16-F10 melanomas. IL-12 has confirmed anti-cancer activity, induces a strong immune response against cancer cells and acts as an anti-angiogenic agent. A major limitation of the use of IL-12 in therapy is its systemic toxicity. The aim of the work was to develop a system in which cytokine may be administered intravenously without toxic side effects. In this study MSC were used as carriers of the IL-12. We confirmed antitumor effectiveness of the cells secreting IL-12 (MSC/IL-12) in primary and metastatic murine melanoma models. We observed inhibition of tumor growth and a significant reduction in the number of metastases in mice after MSC/IL-12 administration. MSC/IL-12 decreased vascular density and increased the number of anticancer M1 macrophages and CD8+ cytotoxic T lymphocytes in tumors of treated mice. To summarize, we showed that MSC are an effective, safe carrier of IL-12 cytokine. Administered systemically they exert therapeutic properties of IL-12 cytokine without toxicity. Therapeutic effect may be a result of pleiotropic (proinflammatory and anti-angiogenic) properties of IL-12 released by modified MSC.

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