scholarly journals Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 654
Author(s):  
Vellingiri Manon Mani ◽  
Arockiam Jeyasundar Parimala Gnana Soundari ◽  
Balamuralikrishnan Balasubramanian ◽  
Sungkwon Park ◽  
Utthapon Issara ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Acute Toxicity ◽  
Endophytic Fungus ◽  
Lethal Dose ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Anti Cancer ◽  
Albino Mice ◽  
Anti Inflammatory

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.

Natural Sesquiterpene Lactones in the Prevention and Treatment of Inflammatory Disorders and cancer: A Systematic Study of this Emerging Therapeutic Approach based on Chemical and Pharmacological Aspect

2020 ◽  
Vol 17 (9) ◽  
pp. 1102-1116
Author(s):  
Sudip Kumar Mandal ◽  
Utsab Debnath ◽  
Amresh Kumar ◽  
Sabu Thomas ◽  
Subhash Chandra Mandal ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Biological Activities ◽  
Sesquiterpene Lactones ◽  
Structural Diversity ◽  
Cancer Drug ◽  
Cancer Drug Discovery ◽  
Anti Cancer ◽  
Drug Discovery Program ◽  
Anti Inflammatory ◽  
Family Based

Background and Introduction: Sesquiterpene lactones are a class of secondary metabolite that contains sesquiterpenoids and lactone ring as pharmacophore moiety. A large group of bioactive secondary metabolites such as phytopharmaceuticals belong to this category. From the Asteraceae family-based medicinal plants, more than 5,000 sesquiterpene lactones have been reported so far. Sesquiterpene lactone-based pharmacophore moieties hold promise for broad-spectrum biological activities against cancer, inflammation, parasitic, bacterial, fungal, viral infection and other functional disorders. Moreover, these moiety based phytocompounds have been highlighted with a new dimension in the natural drug discovery program worldwide after the 2015 Medicine Nobel Prize achieved by the Artemisinin researchers. Objective: These bitter substances often contain an α, β-unsaturated-γ-lactone as a major structural backbone, which in recent studies has been explored to be associated with anti-tumor, cytotoxic, and anti-inflammatory action. Recently, the use of sesquiterpene lactones as phytomedicine has been increased. This study will review the prospect of sesquiterpene lactones against inflammation and cancer. Methods: Hence, we emphasized on the different features of this moiety by incorporating its structural diversity on biological activities to explore structure-activity relationships (SAR) against inflammation and cancer. Results: How the dual mode of action such as anti-inflammatory and anti-cancer has been exhibitedby these phytopharmaceuticals will be forecasted in this study. Furthermore, the correlation of anti-inflammatory and anti-cancer activity executed by the sesquiterpene lactones for fruitful phytotherapy will also be revealed in the present review in the milieu of pharmacophore activity relation and pharmacodynamics study as well. Conclusion: So, these metabolites are paramount in phytopharmacological aspects. The present discussion on the future prospect of this moiety based on the reported literature could be a guide for anti-inflammatory and anti-cancer drug discovery programs for the upcoming researchers.

In vivo protection studies of bis-quaternary 2-(hydroxyimino)-N-(pyridin-3-yl) acetamide derivatives (HNK oximes) against tabun and soman poisoning in Swiss albino mice

2017 ◽  
Vol 36 (12) ◽  
pp. 1270-1285 ◽  
Author(s):  
P Kumar ◽  
D Swami ◽  
DP Nagar ◽  
KP Singh ◽  
J Acharya ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Ache Activity ◽  
Lethal Dose ◽  
Acute Poisoning ◽  
Control Group ◽  
Swiss Albino Mice ◽  
Albino Mice ◽  
Brain Ache Activity ◽  
Protection Index

The study reports antidotal efficacy of three HNK [ bis quaternary 2-(hydroxyimino)-N-(pyridin-3yl) acetamide derivatives] and pralidoxime (2-PAM), against soman and tabun poisoning in Swiss albino mice. Protection index (PI) was determined (treatment doses: HNK oximes, ×0.20 of their median lethal dose (LD50) and 2-PAM, 30 mg/kg, intramuscularly (im)) together with atropine (10 mg/kg, intraperitoneally). Probit log doses with difference of 0.301 log of LD50 of the nerve agents administered and inhibition of acetylcholinesterase (AChE) activity by 50% (IC50) was calculated at optimized time in brain and serum. Using various doses of tabun and soman (subcutaneously (sc)), in multiples of their IC50, AChE reactivation ability of the oximes was studied. Besides, acute toxicity (0.8× LD50, im, 24 h postexposure) of HNK-102 and 2-PAM was also compared by determining biochemical, hematological variables and making histopathological observations. Protection offered by HNK-102 against tabun poisoning was found to be four times higher compared to 2-PAM. However, nearly equal protection was noted with all the four oximes against soman poisoning. HNK-102 reactivated brain AChE activity by 1.5 times more than 2-PAM at IC50 dose of soman and tabun. Acute toxicity studies of HNK-102 and 2-PAM showed sporadic changes in urea, uric acid, aspartate aminotransferase, and so on compared to control group, however, not supported by histopathological investigations. The present investigation showed superiority of newly synthesized HNK-102 oxime over standard 2-PAM, as a better antidote, against acute poisoning of tabun (4.00 times) and soman (1.04 times), in Swiss albino mice.

scholarly journals The nucleotidohydrolases DCTPP1 and dUTPase are involved in the cellular response to decitabine

2016 ◽  
Vol 473 (17) ◽  
pp. 2635-2643 ◽  
Author(s):  
Cristina E. Requena ◽  
Guiomar Pérez-Moreno ◽  
András Horváth ◽  
Beáta G. Vértessy ◽  
Luis M. Ruiz-Pérez ◽  
...  
Keyword(s):  
Thymidylate Synthase ◽  
Cellular Response ◽  
Dna Demethylation ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Strand Breaks ◽  
Anti Cancer ◽  
Synthase Inhibitor ◽  
Dose Dependent ◽  
Cytotoxic Mechanism

Decitabine (5-aza-2′-deoxycytidine, aza-dCyd) is an anti-cancer drug used clinically for the treatment of myelodysplastic syndromes and acute myeloid leukaemia that can act as a DNA-demethylating or genotoxic agent in a dose-dependent manner. On the other hand, DCTPP1 (dCTP pyrophosphatase 1) and dUTPase are two ‘house-cleaning’ nucleotidohydrolases involved in the elimination of non-canonical nucleotides. In the present study, we show that exposure of HeLa cells to decitabine up-regulates the expression of several pyrimidine metabolic enzymes including DCTPP1, dUTPase, dCMP deaminase and thymidylate synthase, thus suggesting their contribution to the cellular response to this anti-cancer nucleoside. We present several lines of evidence supporting that, in addition to the formation of aza-dCTP (5-aza-2′-deoxycytidine-5′-triphosphate), an alternative cytotoxic mechanism for decitabine may involve the formation of aza-dUMP, a potential thymidylate synthase inhibitor. Indeed, dUTPase or DCTPP1 down-regulation enhanced the cytotoxic effect of decitabine producing an accumulation of nucleoside triphosphates containing uracil as well as uracil misincorporation and double-strand breaks in genomic DNA. Moreover, DCTPP1 hydrolyses the triphosphate form of decitabine with similar kinetic efficiency to its natural substrate dCTP and prevents decitabine-induced global DNA demethylation. The data suggest that the nucleotidohydrolases DCTPP1 and dUTPase are factors involved in the mode of action of decitabine with potential value as enzymatic targets to improve decitabine-based chemotherapy.

scholarly journals Biochemical Basis of Anti-Cancer-Effects of Phloretin—A Natural Dihydrochalcone

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 278 ◽  
Author(s):  
Bu Choi
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Human Cancer ◽  
Cancer Drug ◽  
Biochemical Basis ◽  
Human Cancer Cells ◽  
Anti Cancer ◽  
Anti Inflammatory ◽  
Natural Agent ◽  
Growth Of Tumor

Apple is a rich source of bioactive phytochemicals that help improve health by preventing and/or curing many disease processes, including cancer. One of the apple polyphenols is phloretin [2′,4′,6′-Trihydroxy-3-(4-hydroxyphenyl)-propiophenone], which has been widely investigated for its antioxidant, anti-inflammatory and anti-cancer activities in a wide array of preclinical studies. The efficacy of phloretin in suppressing xenograft tumor growth in athymic nude mice implanted with a variety of human cancer cells, and the ability of the compound to interfere with cancer cells signaling, have made it a promising candidate for anti-cancer drug development. Mechanistically, phloretin has been reported to arrest the growth of tumor cells by blocking cyclins and cyclin-dependent kinases and induce apoptosis by activating mitochondria-mediated cell death. The blockade of the glycolytic pathway via downregulation of GLUT2 mRNA and proteins, and the inhibition of tumor cells migration, also corroborates the anti-cancer effects of phloretin. This review sheds light on the molecular targets of phloretin as a potential anti-cancer and anti-inflammatory natural agent.

Anti-Cancer and Antibacterial Effects of Terfezia boudieri-Derived Silver Nanoparticles

2020 ◽  
Vol 23 ◽  
Author(s):  
Hashem Yaghoubi ◽  
Amin Izadpanah ◽  
Shahla Nedaei ◽  
Hossein Akbari ◽  
Elmira Mikaeili Agah ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Chemical Properties ◽  
Chemotherapeutic Agents ◽  
Dependent Manner ◽  
Biomedical Sciences ◽  
Synthesis Time ◽  
Physico Chemical ◽  
Anti Cancer ◽  
Bactericidal Effects ◽  
Terfezia Boudieri

Background: The use of nanoparticles has markedly increased in biomedical sciences. The silver nanoparticles (AgNPs) have been investigated for their applicability to deliver chemotherapeutic agents in cancer treatment. However, the existing chemical and physical methods of synthesizing AgNPs are considered inefficient and expensive, and are fraught with toxicity. Objective: Natural products have emerged as viable candidates for nanoparticle production, including the use of Terfezia boudieri (T. boudieri), a member of the edible truffle family. Accordingly, our goal was to synthesize AgNPs using the aqueous extract of T. boudieri (green synthesized AgNPs). Since certain infectious agents are linked to cancer, we further investigated their potential as anti-cancer and antibacterial agents. Methods: The physico-chemical properties of green synthesized AgNPs were analyzed by UV-Vis, FT-IR, XRD, SEM and TEM. In addition, their potential to inhibit cancer cell (MCF-7 and AGS) proliferation as well as the growth of infectious bacteria were investigated. Synthesis of AgNPs was confirmed by the presence of an absorption peak at 450nm by spectroscopy. Results: The size of nanoparticles ranged between 20-30nm and exerted significant cytotoxicity and bactericidal effects in a concentration and time dependent manner compared to T. boudieri extract alone. Interestingly, synthesis of smaller AgNPs correlated with longer synthesis time and enhanced cytotoxic and bactericidal properties. Conclusion: This study shows that synthesis of smaller AgNPs correlated with longer synthesis time and enhanced cytotoxic and anti-bacterial effects.

Multifunctional effects of honokiol as an anti-inflammatory and anti-cancer drug in human oral squamous cancer cells and xenograft

Biomaterials ◽  
2015 ◽  
Vol 53 ◽  
pp. 274-284 ◽  
Author(s):  
Jin Hyoung Cho ◽  
Young-Joo Jeon ◽  
Seon-Min Park ◽  
Jae-Cheon Shin ◽  
Tae-Hoon Lee ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cancer Drug ◽  
Anti Cancer ◽  
Squamous Cancer ◽  
Anti Inflammatory

scholarly journals Essential Oil from Zingiber ottensii Induces Human Cervical Cancer Cell Apoptosis and Inhibits MAPK and PI3K/AKT Signaling Cascades

Plants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1419
Author(s):  
Jirapak Ruttanapattanakul ◽  
Nitwara Wikan ◽  
Kittinan Chinda ◽  
Thanathorn Jearanaikulvanich ◽  
Napatsorn Krisanuruks ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Essential Oil ◽  
Western Blot ◽  
Cancer Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Growth And Survival ◽  
Anti Cancer ◽  
Cervical Cancer Cells ◽  
Human Cervical Cancer

Zingiber ottensii (ZO) is a local plant in Thailand and has been used as a Thai traditional therapy for many conditions. ZO has been reported to exhibit many pharmacological effects, including anti-cancer activity. Nevertheless, its anti-cancer effects explored at the signaling level have not been elucidated in cervical cancer, which is one of the leading causes of fatality in females. We discovered that the essential oil of ZO significantly increased the apoptosis of human cervical cancer cells (HeLa) after 24 h of treatment in a concentration-dependent manner. Our data also clearly demonstrated that ZO essential oil reduced IL-6 levels in the culture supernatants of the cancer cells. Moreover, Western blot analysis clearly verified that cells were induced to undergo apoptotic death via caspase activation upon treatment with ZO essential oil. Interestingly, immunofluorescence studies and Western blot analyses showed that ZO essential oil suppressed epidermal growth factor (EGF)-induced pAkt and pERK1/2 signaling pathway activation. Together, our study demonstrates that ZO essential oil can reduce the proliferation and survival signaling of HeLa cervical cancer cells. Our study provides convincing data that ZO essential oil suppresses the growth and survival of cervical cancer cells, and it may be a potential choice for developing an anti-cancer agent for treating certain cervical cancers.

scholarly journals Comparison of responsiveness to cancer development and anti-cancer drug in three different C57BL/6N stocks

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Mi Ju Kang ◽  
Ji Eun Kim ◽  
Ji Won Park ◽  
Hyeon Jun Choi ◽  
Su Ji Bae ◽  
...  
Keyword(s):  
Animal Models ◽  
Tumor Tissue ◽  
Tumor Model ◽  
Cancer Drug ◽  
Dependent Manner ◽  
Cancer Drugs ◽  
Ki 67 ◽  
Anti Cancer ◽  
Dose Dependent ◽  
Syngeneic Model

Abstract In our efforts to understand the systemic features of tumors, the importance of animal models is increasing due to the recent growth in the development of immunotherapy and targeted therapies. This has resulted in increased attention towards tumor animal models using C57BL/6N, which are mainly used in immunological studies. In this study, the C57BL/6NKorl stock and two other commercial stocks (C57BL/6NA and C57BL/N6B) are evaluated by comparing the occurrence of tumors using the syngeneic model; furthermore, we compare the response to anti-cancer drugs in the syngeneic model by evaluating survival, growth of tumors, proliferation and molecular biology analysis. In the syngeneic model using LLC (Lewis lung carcinoma) cells, the survival of mice and growth of the tumor showed a better response in the C57BL/6NKorl stock, and was dependent on the cell concentration of the dosing tumor, as compared to the other C57BL/6N stocks. However, the Ki-67 staining showed only little difference in cell proliferation within the tumor tissue each mouse stocks. Comparing the sensitivity to anti-cancer drug by examining changes in growth, volume and weight revealed that cisplatin treatment for tumor-bearing C57BL/6NKorl was more dependent on concentration. The Ki-67 staining, however, showed no difference among the C57BL/6N stocks after cisplatin treatment. The expressions of p27 and p53 tumor suppressor proteins, caspase-3 and Bax showed dose-dependent increase after exposure to cisplatin, whereas the expression of Bcl-2 was reduced in a dose-dependent manner. Furthermore, the expressions of MMP-2 and VEGF involved in metastasis, as well as inflammatory genes IL-1β, IL-6 and IL-10, showed dose-dependent decrease in tumor tissue after cisplatin exposure. Differences observed among the C57BL/6N stocks were not significant. Taken together, our studies reveal that C57BL/6NKorl has the potential of being a useful biological resource established in Korea, as it does not differ from the two commercially available C57BL/6N stocks when considering response to tumor generation and sensitivity to anti-cancer drugs using the syngeneic tumor model.

Role of Azoles in Cancer Prevention and Treatment: Present and Future Perspectives

2018 ◽  
Vol 18 (1) ◽  
pp. 46-56 ◽  
Author(s):  
Khurshid Ahmad ◽  
Mohd Kalim A. Khan ◽  
Mohammad Hassan Baig ◽  
Mohd Imran ◽  
Girish Kumar Gupta
Keyword(s):  
Cancer Prevention ◽  
Chemotherapeutic Agents ◽  
Cancer Drug ◽  
Future Perspectives ◽  
Multifactorial Diseases ◽  
Cancer Management ◽  
Cancer Drug Resistance ◽  
Anti Cancer ◽  
Prevention And Treatment

Background: Cancer has gradually become one of the leading causes of death worldwide. The incidence of cancer among the population has increased alarmingly over the last two decades, primarily due to an increasing population of immune-compromised patients and the continuing rise in anti-cancer drug resistance. Azole found privileged structure in medicinal chemistry and pharmaceutical industry and also found to be showing antioxidant; antimicrobial, anthelmintic, anticancer, antiviral, anti-parasitic, anti-inflammatory, anti-HIV, and antihypertensive activities. Objective: In this review, we highlight some areas of current interest in context to azoles and their derivatives as potential chemotherapeutic agents and inhibitors. Method: A comprehensive literature search was performed for writing this review. An updated view on different derivatives of azoles and use in cancer management has been discussed. Results: Here we have discussed the present scenario of azoles and their derivatives as potential chemotherapeutic agents and inhibitors. Along with, the future perspectives of azoles in cancer prevention and treatment are also discussed. Conclusion: The information provided in this review might be useful to researchers in designing of novel and potent multifunctional azole analogues for the treatment of cancer and other multifactorial diseases.

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