scholarly journals Extracts of Tagetes erecta exhibit potential cytotoxic and antitumor activity that could be employed as a promising therapeutic agent against cancer: A study involving in vitro and in vivo approach

2021 ◽  
pp. 100187
Author(s):  
Dharmeswar Barhoi ◽  
Puja Upadhaya ◽  
Sweety Nath Barbhuiya ◽  
Anirudha Giri ◽  
Sarbani Giri
Keyword(s):  
Antitumor Activity ◽  
Therapeutic Agent ◽  
Tagetes Erecta ◽  
Promising Therapeutic Agent

scholarly journals Pharmacological Activity of Garcinia indica (Kokum): An Updated Review

2021 ◽  
Vol 14 (12) ◽  
pp. 1338
Author(s):  
Sung Ho Lim ◽  
Ho Seon Lee ◽  
Chang Hoon Lee ◽  
Chang-Ik Choi
Keyword(s):  
Traditional Medicine ◽  
Pharmacological Activity ◽  
Therapeutic Agent ◽  
Industrial Applications ◽  
Pharmacological Activities ◽  
Garcinia Indica ◽  
Hydroxycitric Acid ◽  
Promising Therapeutic Agent

Garcinia indica (commonly known as kokum), belonging to the Clusiaceae family (mangosteen family), is a tropical evergreen tree distributed in certain regions of India. It has been used in culinary and industrial applications for a variety of purposes, including acidulant in curries, pickles, health drinks, wine, and butter. In particular, G. indica has been used in traditional medicine to treat inflammation, dermatitis, and diarrhea, and to promote digestion. According to several studies, various phytochemicals such as garcinol, hydroxycitric acid (HCA), cyanidin-3-sambubioside, and cyanidin-3-glucoside were isolated from G. indica, and their pharmacological activities were published. This review highlights recent updates on the various pharmacological activities of G. indica. These studies reported that G. indica has antioxidant, anti-obesity, anti-arthritic, anti-inflammatory, antibacterial, hepatoprotective, cardioprotective, antidepressant and anxiolytic effects both in vitro and in vivo. These findings, together with previously published reports of pharmacological activity of various components isolated from G. indica, suggest its potential as a promising therapeutic agent to prevent various diseases.

scholarly journals A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Motoo Saito ◽  
Kohei Nishitani ◽  
Hanako O. Ikeda ◽  
Shigeo Yoshida ◽  
Sachiko Iwai ◽  
...  
Keyword(s):  
Cell Death ◽  
Er Stress ◽  
Therapeutic Agent ◽  
Articular Chondrocytes ◽  
Cartilage Explants ◽  
Chondrocyte Death ◽  
Post Traumatic ◽  
Promising Therapeutic Agent

AbstractPost-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA.

scholarly journals Aspirin suppresses chemoresistance and enhances antitumor activity of 5-Fu in 5-Fu-resistant colorectal cancer by abolishing 5-Fu-induced NF-κB activation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jinbo Fu ◽  
Yiming Xu ◽  
Yushan Yang ◽  
Yun Liu ◽  
Lulu Ma ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Antitumor Activity ◽  
Therapeutic Agent ◽  
Inhibitory Effect ◽  
Antitumor Activities ◽  
Tumor Cell Apoptosis ◽  
Tumor Growth And Metastasis ◽  
Resistant Cells

AbstractChemoresistance to 5-fluorouracil (5-Fu)-based chemotherapy is a leading obstacle in achieving effective treatment for colorectal cancer (CRC). Typically, NF-κB activation induced by the chemotherapeutics themselves is an important cause resulting in chemoresistance. Specifically, NF-κB activation can inhibit tumor cell apoptosis and induce chemoresistance. Drugs that can prevent NF-κB activation induced by chemotherapeutics are urgently needed to overcome chemoresistance. Obviously, aspirin is one of these agents, which has been demonstrated to possess antitumor activities and as an inhibitor of NF-κB. The current study aimed to investigate whether aspirin was able to overcome the chemoresistance to 5-Fu in CRC, together with the potential synergistic mechanisms. Our results suggested that aspirin remarkably potentiated the inhibitory effect of 5-Fu on the growth and invasion of resistant cells in vitro. In vivo, aspirin markedly enhanced the antitumor activity of 5-Fu in suppressing tumor growth and metastasis, and down-regulating the expression of NF-κB-regulated genes in the 5-Fu-resistant cells. Obviously, aspirin completely eradicated the 5-Fu-induced NF-κB activation, without inducing pronounced adverse effects. Taken together, findings in this study suggest that aspirin can reverse chemoresistance and potentiate the antitumor effect of 5-Fu, which is achieved through abolishing the 5-Fu-induced NF-κB activation, suggesting that aspirin may be a promising adjuvant therapeutic agent for CRC.

scholarly journals PROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Chengcheng Shi ◽  
Huapeng Zhang ◽  
Penglei Wang ◽  
Kai Wang ◽  
Denghui Xu ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Bet Inhibitors ◽  
Oncogenic Protein ◽  
Bet Protein ◽  
Massive Apoptosis ◽  
Promising Therapeutic Agent

Abstract Targeting oncogenic proteins for degradation using proteolysis-targeting chimera (PROTAC) recently has drawn increasing attention in the field of cancer research. Bromodomain and extra-terminal (BET) family proteins are newly identified cancer-related epigenetic regulators, which have a role in the pathogenesis and progression of osteosarcoma. In this study, we investigated the in vitro and in vivo anti-osteosarcoma activity by targeting BET with a PROTAC molecule BETd-260. The results showed that BETd-260 completely depletes BET proteins and potently suppresses cell viability in MNNG/HOS, Saos-2, MG-63, and SJSA-1 osteosarcoma cell lines. Compared with BET inhibitors HJB-97 and JQ1, the activity of BETd-260 increased over 1000 times. Moreover, BETd-260 substantially inhibited the expression of anti-apoptotic Mcl-1, Bcl-xl while increased the expression of pro-apoptotic Noxa, which resulted in massive apoptosis in osteosarcoma cells within hours. In addition, pro-oncogenic protein c-Myc also was substantially inhibited by BETd-260 in the OS cells. Of note, BETd-260 induced degradation of BET proteins, triggered apoptosis in xenograft osteosarcoma tumor tissue, and profoundly inhibited the growth of cell-derived and patient-derived osteosarcoma xenografts in mice. Our findings indicate that BET PROTACs represent a promising therapeutic agent for human osteosarcoma.

In vivo efficacy of olorofim against systemic scedosporiosis and lomentosporiosis

2021 ◽  
Author(s):  
S. Seyedmousavi ◽  
Y. C. Chang ◽  
J. H. Youn ◽  
D. Law ◽  
M. Birch ◽  
...  
Keyword(s):  
Post Infection ◽  
Therapeutic Agent ◽  
Intraperitoneal Administration ◽  
Scedosporium Apiospermum ◽  
Pseudallescheria Boydii ◽  
Target Organs ◽  
Fungal Dna ◽  
Promising Therapeutic Agent

Clinically relevant members of the Scedosporium / Pseudallescheria species complex and Lomentospora prolificans are generally resistant against currently available systemic antifungal agents in vitro and the infection due to these species is difficult to treat. We studied the in vivo efficacy of a new fungicidal agent olorofim (formerly F901318) against scedosporiosis and lomentosporiosis in neutropenic animals. Cyclophosphamide immunosuppressed CD-1 mice infected by Scedosporium apiospermum , Pseudallescheria boydii ( Scedosporium boydii ) and Lomentospora prolificans were treated by intraperitoneal administration of olorofim (15 mg/kg every 8 h for 9 days). The efficacy of olorofim treatment was assessed by the survival rate at 10 days post infection, levels of serum (1-3)-β-d-glucan (BG), histopathology, and fungal burden of kidneys 3 days post infection. Olorofim therapy significantly improved survival compared to the untreated controls; 80%, 100% and 100% of treated mice survived infection by Scedosporium apiospermum , Pseudallescheria boydii , and Lomentospora prolificans, respectively while less than 20% of the control mice (PBS-treated) survived at 10 days post infection. In the olorofim-treated neutropenic CD-1 mice infected with all three species, serum BG levels were significantly suppressed and fungal DNA detected in the target organs was significantly lower than controls. Furthermore, histopathology of kidneys revealed no or only few lesions with hyphal elements in the olorofim-treated mice, while numerous fungal hyphae were present in control mice. These results indicate olorofim to be a promising therapeutic agent for systemic scedosporiosis/lomentosporiosis, a devastating emerging fungal infection difficult to treat with currently available antifungals.

scholarly journals Targeting Dopamine Receptor D2 by Imipridone Suppresses Uterine Serous Cancer Malignant Phenotype

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2436 ◽  
Author(s):  
Wen Hu ◽  
Li Zhang ◽  
Sammy Ferri-Borgogno ◽  
Suet-Ying Kwan ◽  
Kelsey E. Lewis ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Survival Rates ◽  
Metabolic Reprogramming ◽  
Recurrence Rates ◽  
Poor Overall Survival ◽  
Orally Bioavailable ◽  
Induced Apoptosis ◽  
Promising Therapeutic Agent

Uterine serous cancer (USC) is an aggressive subtype of endometrial cancer, with poor survival and high recurrence rates. The development of novel and effective therapies specific to USC would aid in its management. However, few studies have focused solely on this rare subtype. The current study demonstrated that the orally bioavailable, investigational new drug and novel imipridone ONC206 suppressed USC cell proliferation and induced apoptosis both in vitro and in vivo. Disruption of the DRD2-mediated p38MAPK/ERK/PGC-1α network by ONC206 led to metabolic reprogramming and suppression of both glycolysis and oxidative phosphorylation. ONC206 also synergized with paclitaxel in reducing USC cell viability. In addition, DRD2 overexpression correlated with poor overall survival in patients. This study provides the first evidence that ONC206 induced metabolic reprogramming in USC cells and is a promising therapeutic agent for USC treatment. These findings support further development of ONC206 as a promising therapeutic agent and improves survival rates in patients with USC.

scholarly journals The Protective Effect of Cordycepin on D-Galactosamine/Lipopolysaccharide-Induced Acute Liver Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jin Li ◽  
Liping Zhong ◽  
Haibo Zhu ◽  
Fengzhong Wang
Keyword(s):  
Protective Effect ◽  
Therapeutic Agent ◽  
Cytokine Production ◽  
Hepatocyte Apoptosis ◽  
Apoptosis And Necrosis ◽  
And Oxidative Stress ◽  
Lps Treatment ◽  
Promising Therapeutic Agent

As the major active ingredient ofCordyceps militaris, cordycepin (3′-deoxyadenosine) has been well documented to alleviate inflammation and oxidative stress both in vitro and in vivo. To explore the potential protective effect of cordycepin in fulminant hepatic failure, mice were pretreated with cordycepin for 3 weeks followed by D-galactosamine (GalN)/lipopolysaccharide (LPS) injection. Then we found cordycepin (200 mg/kg) administration elevated survival rate, improved liver function, and suppressed hepatocyte apoptosis and necrosis in mice with severe hepatic damage by GalN/LPS treatment. Further, cordycepin inhibited hepatic neutrophil and macrophage infiltration and prevented proinflammatory cytokine production possibly through suppressing TLR4 and NF-κB signaling transduction. The blockade of reactive oxygen species (ROS) and lipid peroxidation production by cordycepin was associated with the decrease of NAD(P)H oxidase (NOX) activity. Besides, cordycepin significantly prevented excessive autophagy induced by GalN/LPS in the liver. These data suggested that cordycepin could be a promising therapeutic agent for GalN/LPS-induced hepatotoxicity.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

Surface Labeling with Adhesion Protein FimH Improves Binding of Immunotherapeutic Agent Salmonella Ty21a to the Bladder Epithelium

2020 ◽  
pp. 1-12
Author(s):  
Maroeska J. Burggraaf ◽  
Lisette Waanders ◽  
Mariska Verlaan ◽  
Janneke Maaskant ◽  
Diane Houben ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Antitumor Activity ◽  
Bladder Wall ◽  
Bladder Epithelium ◽  
Modest Improvement ◽  
Adhesion Protein ◽  
Survival Experiment ◽  
Muscle Invasive

BACKGROUND: Bladder cancer is the ninth most common cancer in men. 70% of these tumors are classified as non-muscle invasive bladder cancer and those patients receive 6 intravesical instillations with Mycobacterium bovis BCG after transurethral resection. However, 30% of patients show recurrences after treatment and experience severe side effects that often lead to therapy discontinuation. Recently, another vaccine strain, Salmonella enterica typhi Ty21a, demonstrated promising antitumor activity in vivo. Here we focus on increasing bacterial retention in the bladder in order to reduce the number of instillations required and improve antitumor activity. OBJECTIVE: To increase the binding of Ty21a to the bladder wall by surface labeling of the bacteria with adhesion protein FimH and to study its effect in a bladder cancer mouse model. METHODS: Binding of Ty21a with surface-labeled FimH to the bladder wall was analyzed in vitro and in vivo. The antitumor effect of a single instillation of Ty21a+FimH in treatment was determined in a survival experiment. RESULTS: FimH-labeled Ty21a showed significant (p <  0.0001) improved binding to mouse and human cell lines in vitro. Furthermore, FimH labeled bacteria showed ∼5x more binding to the bladder than controls in vivo. Enhanced binding to the bladder via FimH labeling induced a modest improvement in median but not in overall mice survival. CONCLUSIONS: FimH labeling of Ty21a significantly improved binding to bladder tumor cells in vitro and the bladder wall in vivo. The improved binding leads to a modest increase in median survival in a single bladder cancer mouse study.

Sign in / Sign up

Export Citation Format

Share Document