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Journal ArticleDOI: 10.1080/07391102.2020.1734482

Atranorin, an antimicrobial metabolite from lichen Parmotrema rampoddense exhibited in vitro anti-breast cancer activity through interaction with Akt activity.

04 Mar 2021-Journal of Biomolecular Structure & Dynamics (Taylor & Francis)-Vol. 39, Iss: 4, pp 1248-1258
Abstract: Atranorin (ATR), lichenized secondary metabolite and depside molecule with several biological potentials such as antimicrobial, anticancer, anti-inflammatory, antinociceptive, wound healing and pho...

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Topics: Metabolite (55%), Depside (52%)
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8 results found



Open accessJournal ArticleDOI: 10.3390/JOF7040252
26 Mar 2021-Journal of Fungi
Abstract: Despite the fascinating biology of lichens, such as the symbiotic association of lichen-forming fungi (mycobiont) with their photosynthetic partners and their ability to grow in harsh habitats, lack of genetic tools manipulating mycobiont has hindered studies on genetic mechanisms underpinning lichen biology Thus, we established an Agrobacterium tumefaciens-mediated transformation (ATMT) system for genetic transformation of a mycobiont isolated from Cladonia macilenta A set of combinations of ATMT conditions, such as input biomass of mycobiont, co-cultivation period with Agrobacterium cells, and incubation temperature, were tested to identify an optimized ATMT condition for the C macilenta mycobiont As a result, more than 10 days of co-cultivation period and at least 2 mg of input biomass of the mycobiont were recommended for an efficient ATMT, owing to extremely slow growth rate of mycobionts in general Moreover, we examined T-DNA copy number variation in a total of 180 transformants and found that 88% of the transformants had a single copy T-DNA insertion To identify precise T-DNA insertion sites that interrupt gene function in C macilenta, we performed TAIL-PCR analyses for selected transformants A hypothetical gene encoding ankyrin repeats at its C-terminus was interrupted by T-DNA insertion in a transformant producing dark-brown colored pigment Although the identification of the pigment awaits further investigation, this proof-of-concept study demonstrated the feasibility of use of ATMT in construction of a random T-DNA insertion mutant library in mycobionts for studying genetic mechanisms behind the lichen symbiosis, stress tolerance, and secondary metabolite biosynthesis

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Topics: Agrobacterium (52%)

2 Citations


Journal ArticleDOI: 10.1016/J.JEP.2020.113437
Abstract: Ethno-pharmacological relevance A natural ursolic compound, 2β,3β,23-trihydroxy-urs-12-ene-28-olic acid (TUA) was isolated from the root of Actinidia fulvicoma Hance. (A. fulvicoma Radix), which is used as a traditional hebal medicine to cure innominate inflammation of unknown origin of the digestive tract in the She nationality. Aim of the study: The aim of present study was to investigate the effects of TUA on gastric cancer and to clarify the potential mechanisms in human gastric cancer cell line BGC823 cells in vitro and in vivo. Materials and methods Cell proliferation, apoptosis, cell cycle, autophagy were all measured by MTS assay, flow cytometry following exposure to TUA. The mRNA expressions of PI3K, AKT, mTOR, P70S6K, Survivin and the protein expressions of p-PI3K, p-AKT, p-mTOR, p-P70S6K, Survivin were determined by qRT-PCR and Western blotting analysis, respectively. In vivo antitumor activity of TUA was assessed in a xenograft model. Results In vitro studies showed that TUA significantly suppressed the viability of BGC823 cells in a concentration- and time-dependent manner but not GES-1 non-tumorigenic human gastric epithelial cells. TUA also significantly increased the apoptosis rate and the sub G2 population by cell cycle analysis in a concentration dependent manner. Exposure to TUA decreased PI3K, AKT, mTOR, P70S6K, Survivin mRNA, inhibited the phosphorylation of major receptors involved in autophagy and apoptosis, such as PI3K, AKT, mTOR and P70S6K, while reduced the expression of Survivin in BGC cells. In vivo studies showed that TUA decreased tumor volume and tumor weight and also down regulated the autophagy-related proteins expression. Conclusions TUA occupies underlying antitumor effects, the potential mechanisms may involve the suppression of mTOR/Survivin pathways connected to autophagy and the activation of apoptotic pathways in gastric cancer cells.

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Topics: PI3K/AKT/mTOR pathway (58%), Survivin (58%), Protein kinase B (55%) ... show more

2 Citations


Open accessJournal ArticleDOI: 10.3390/MOLECULES26041121
20 Feb 2021-Molecules
Abstract: The present study provides new data concerning the chemical characterisation of Physcia mediterranea Nimis, a rare Mediterranean species belonging to the family Physciaceae. The phytochemical screening was carried out using GC-MS, HPLC-ESI-MS-MS, and NMR techniques. Hot extraction of n-hexane was carried out, followed by separation of the part insoluble in methanol: wax (WA-hex), from the part soluble in methanol (ME-hex). GC-MS analysis of the ME-hex part revealed the presence of methylbenzoic acids such as sparassol and atraric acid and a diterpene with a kaurene skeleton which has never been detected before in lichen species. Out of all the compounds identified by HPLC-ESI-MS-MS, sixteen compounds are common between WA-hex and ME-hex. Most are aliphatic fatty acids, phenolic compounds and depsides. The wax part is characterised by the presence of atranorin, a depside of high biological value. Proton 1H and carbon 13C NMR have confirmed its identification. Atranol, chloroatranol (depsides compound), Ffukinanolide (sesquiterpene lactones), leprolomin (diphenyl ether), muronic acid (triterpenes), and ursolic acid (triterpenes) have also been identified in ME-hex. The results suggested that Physcia mediterranea Nimis is a valuable source of bioactive compounds that could be useful for several applications as functional foods, cosmetics, and pharmaceuticals.

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Topics: Physcia (57%), Depside (56%)

1 Citations


Open accessJournal ArticleDOI: 10.3390/APP10196981
06 Oct 2020-Applied Sciences
Abstract: Molecular docking in the pharmaceutical industry is a powerful in silico approach for discovering novel therapies for unmet medical needs predicting drug–target interactions. It not only provides binding affinity between drugs and targets at the atomic level, but also elucidates the fundamental pharmacological properties of specific drugs. The purpose of this review was to illustrate newer and emergent uses of docking when combined with in vitro techniques for drug discovery in metastatic breast cancer. We grouped the selected articles into five main categories; namely, systematic repositioning of drugs, natural drugs, new synthesized molecules, combinations of drugs, and drug latentiation. We focused on new promising drugs that have a good affinity with their targets, thus inducing a favorable biological response. This review suggests that the integration of molecular docking and in vitro studies can accelerate cancer drug discovery showing a good consistency of the results between the two approaches.

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Topics: Docking (molecular) (54%), Drug discovery (54%)

1 Citations


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45 results found


Open accessJournal ArticleDOI: 10.3322/CAAC.20107
Ahmedin Jemal1, Freddie Bray2, Jacques Ferlay2, Elizabeth Ward1  +1 moreInstitutions (2)
Abstract: The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

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Topics: Epidemiology of cancer (69%), Cancer (67%), Preventive healthcare (63%) ... show more

51,138 Citations


Journal ArticleDOI: 10.1002/IJC.25516
Jacques Ferlay1, Hai-Rim Shin1, Freddie Bray1, David Forman1  +2 moreInstitutions (3)
Abstract: Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed.

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Topics: Causes of cancer (61%), Cancer (60%), Breast cancer (53%) ... show more

20,379 Citations


Open accessJournal ArticleDOI: 10.1158/1078-0432.CCR-08-0144
Min H. Kang1, C. Patrick ReynoldsInstitutions (1)
Abstract: Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals transmitted by cellular damage (including antineoplastic drugs) or cytokine deprivation can initiate apoptosis via the intrinsic apoptotic pathway. It is controversial whether some BH3-domain proteins (Bim or tBid) directly activate multidomain pro-apoptotic proteins (e.g., Bax and Bak) or act via inhibition of those anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that stabilize pro-apoptotic proteins. Overexpression of anti-apoptotic Bcl-2 family members has been associated with chemotherapy resistance in various human cancers, and preclinical studies have shown that agents targeting anti-apoptotic Bcl-2 family members have preclinical activity as single agents and in combination with other antineoplastic agents. Clinical trials of several investigational drugs targeting the Bcl-2 family (oblimersen sodium, AT-101, ABT-263, GX15-070) are ongoing. Here, we review the role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl-2 family of proteins.

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Topics: Obatoclax (52%)

872 Citations


Journal ArticleDOI: 10.1016/J.BBAPAP.2003.11.009
Abstract: Protein phosphorylation and dephosphorylation play a major role in intracellular signal transduction activated by extracellular stimuli. Protein kinase B (PKB/Akt) is a central player in the signal transduction pathways activated in response to growth factors or insulin and is thought to contribute to several cellular functions including nutrient metabolism, cell growth and apoptosis. Recently, several significant publications have described novel mechanisms used to regulate PKB. Since the alteration of PKB activity is associated with several human diseases, including cancer and diabetes, understanding PKB regulation is an important task if we are to develop successful therapeutics.

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Topics: mTORC2 (63%), Intracellular signal transduction (58%), Protein kinase B (57%) ... show more

709 Citations


Open accessJournal ArticleDOI: 10.1016/J.GDE.2009.11.002
Abstract: The phosphoinositide 3-kinase (PI3K) pathway is activated in a variety of different human cancers, and inhibitors of this pathway are under active development as anti-cancer therapeutics. In this review, we discuss the data supporting the use of PI3K pathway inhibitors in genetically and clinically defined cancers. This review focuses on their efficacy as single agents and in combination with other targeted therapies, specifically those targeting the MEK-ERK signaling pathway.

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496 Citations