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https://www.readbyqxmd.com/read/29160846/a-triphenylphosphonium-functionalized-mitochondriotropic-nanocarrier-for-efficient-co-delivery-of-doxorubicin-and-chloroquine-and-enhanced-antineoplastic-activity
#1
Katerina N Panagiotaki, Zili Sideratou, Spiros A Vlahopoulos, Maria Paravatou-Petsotas, Michael Zachariadis, Nikolas Khoury, Vassilis Zoumpourlis, Dimitris Tsiourvas
Drug delivery systems that target subcellular organelles and, in particular, mitochondria are considered to have great potential in treating disorders that are associated with mitochondrial dysfunction, including cancer or neurodegenerative diseases. To this end, a novel hyperbranched mitochondriotropic nanocarrier was developed for the efficient co-delivery of two different (both in chemical and pharmacological terms) bioactive compounds. The carrier is based on hyperbranched poly(ethyleneimine) functionalized with triphenylphosphonium groups that forms ~100 nm diameter nanoparticles in aqueous media and can encapsulate doxorubicin (DOX), a well-known anti-cancer drug, and chloroquine (CQ), a known chemosensitizer with arising potential in anticancer medication...
November 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29160745/the-unveiling-of-the-warburg-effect-and-the-inscribed-innovative-approach-to-a-radical-non-toxic-anticancer-therapy
#2
Olivia Crociani, Ilaria Marzi, Maria Grazia Cipolleschi, Antonella Mannini, Massimo Contini, Massimo Olivotto
The purpose of this research has been deciphering the Warburg paradox, the biochemical enigma unsolved since 1923. This paradox consists of the aerobic pyruvate conversion to lactate brought about by anaplastic cancer, through the metabolic pathway known as aerobic glycolysis. This pathway implies a heavy energetic waste. We solved the enigma by demonstrating that its specific character, i.e. the forced aerobic lactate exportation, represents a crucial metabolic device to counteract the cytotoxic effect produced by an excess of pyruvate at the connection of glycolysis with the Krebs cycle...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29157834/16-hydroxycleroda-3-13-dien-15-16-olide-inhibits-the-proliferation-and-induces-mitochondrial-dependent-apoptosis-through-akt-mtor-and-mek-erk-pathways-in-human-renal-carcinoma-cells
#3
Cheng Liu, Wei-Chang Lee, Bu-Miin Huang, Yi-Chen Chia, Yu-Chi Chen, Yung-Chia Chen
BACKGROUND: Renal cell carcinoma (RCC) is well known that it cannot be treated with traditional chemotherapy or radiotherapy. 16-Hydroxycleroda-3,13-dien-15,16-olide (CD), isolated from Polyalthia longifolia Benth. & Hook. f. var. pendula had been reported to display significant efficacy against cancer cell lines. PURPOSE: To determine the anti-tumour activities of CD in two clear cell type RCC (ccRCC) cell lines (A-498 and 786-O). In addition, the underlying mechanisms were also examined...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157817/cardioprotective-action-of-the-aqueous-extract-of-terminalia-arjuna-bark-against-toxicity-induced-by-doxorubicin
#4
Sarah Bishop, Shi J Liu
BACKGROUND: The aqueous extract of Terminalia arjuna (TA) bark (TAAqE) has been shown to have a direct inotropic effect on ventricular myocytes. Active constituents of TAAqE contain various flavonoids and proanthocyanidins, some of which are known to have antioxidant activities. Whether TAAqE affords a cardioprotective action against oxidative stress (OS) remains unclear. PURPOSE: Increased OS is one of the major mechanisms underlying cardiotoxicity induced by doxorubicin (DOX), a commonly-used anticancer agent...
December 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29157537/special-issue-mitochondria-in-cancer
#5
EDITORIAL
Keshav K Singh, Josephine S Modica-Napolitano
No abstract text is available yet for this article.
December 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29154934/cephalostatin-1-analogues-activate-apoptosis-via-the-endoplasmic-reticulum-stress-signaling-pathway
#6
Lubna H Tahtamouni, Mansour M Nawasreh, Zainab A Al-Mazaydeh, Rema A Al-Khateeb, Reem N Abdellatif, Randa M Bawadi, James R Bamburg, Salem R Yasin
The current study was conducted to compare the cytotoxicity of two stereospecific cephalostatin 1 analogues (CAs) against several human normal cell types and cancer cell lines and to determine their cytotoxic mechanism. Both CA analogues induced apoptosis and were cytotoxic with 50% growth inhibition (GI50) at ~1µM or less in six human cancer cell lines but neither analogue at 10µM killed more than 14% of any of three types of normal human cells suggesting their cytotoxicity is cancer-specific. CA treatment inhibited clonogenic tumor growth and activated caspase 3 and 9 but not caspase 8...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29151954/cpt1c-regulated-by-ampk-promotes-papillary-thyroid-carcinomas-cells-survival-under-metabolic-stress-conditions
#7
Rui Wang, Yajun Cheng, Dongwei Su, Boshen Gong, Xiaobo He, Xinyu Zhou, Zhijun Pang, Lingtao Cheng, Yuelei Chen, Zhenzhen Yao
Background: Cancer cells have to take metabolic transformation in tumor progression when facing need of increased energy and adequate vascularization. However, molecular mechanism is not fully known. In this study, we showed that expression of carnitine palmitoyltransferase 1C (Cpt1c), as a member of the gate-keeper enzymes , which transferring long-chain fatty acids into mitochondria to further oxidation, which is regulated by AMPK promotes papillary thyroid carcinomas cells survival under metabolic stress conditions...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151915/phloretin-induces-apoptosis-of-human-esophageal-cancer-via-a-mitochondria-dependent-pathway
#8
Hongtao Duan, Ruixuan Wang, Xiaolong Yan, Honggang Liu, Yong Zhang, Deguang Mu, Jing Han, Xiaofei Li
2,4,6-trihydroxy-3-(4-hydroxyphenyl)-propiophenone (phloretin) is found in apple tree leaves and the Manchurian apricot, and is a potent compound that exhibits anti-inflammatory, antioxidant and antitumor activities. However, the effect of phloretin on esophageal cancer cells is not well-defined. The present study aimed to examine whether and how phloretin induced apoptosis in human esophageal cancer cells. EC-109 cells were cultured in Dulbecco's modified Eagle's medium and incubated with 60, 70, 80, 90 and 100 µg/ml phloretin for 6, 12, 24 and 48 h...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29150934/the-current-status-and-perspectives-regarding-the-clinical-implication-of-intracellular-calcium-in-breast-cancer
#9
REVIEW
Amir Tajbakhsh, Alireza Pasdar, Mehdi Rezaee, Mostafa Fazeli, Saman Soleimanpour, Seyed Mahdi Hassanian, Zahra FarshchiyanYazdi, Tayebe Younesi Rad, Gordon A Ferns, Amir Avan
Calcium ions (Ca(2+) ) act as second messengers in intracellular signaling. Ca(2+) pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca(2+) as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca(2+) also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150439/suppression-of-fip200-and-autophagy-by-tumor-derived-lactate-promotes-na%C3%A3-ve-t-cell-apoptosis-and-affects-tumor-immunity
#10
Houjun Xia, Wei Wang, Joel Crespo, Ilona Kryczek, Wei Li, Shuang Wei, Zhaoqun Bian, Tomasz Maj, Mingxiao He, Rebecca J Liu, Youwen He, Ramandeep Rattan, Adnan Munkarah, Jun-Lin Guan, Weiping Zou
Naïve T cells are poorly studied in cancer patients. We report that naïve T cells are prone to undergo apoptosis due to a selective loss of FAK family-interacting protein of 200 kDa (FIP200) in ovarian cancer patients and tumor-bearing mice. This results in poor antitumor immunity via autophagy deficiency, mitochondria overactivation, and high reactive oxygen species production in T cells. Mechanistically, loss of FIP200 disables the balance between proapoptotic and antiapoptotic Bcl-2 family members via enhanced argonaute 2 (Ago2) degradation, reduced Ago2 and microRNA1198-5p complex formation, less microRNA1198-5p maturation, and consequently abolished microRNA1198-5p-mediated repression on apoptotic gene Bak1 Bcl-2 overexpression and mitochondria complex I inhibition rescue T cell apoptosis and promoted tumor immunity...
November 17, 2017: Science Immunology
https://www.readbyqxmd.com/read/29150352/dysregulation-of-mrna-translation-and-energy-metabolism-in-cancer
#11
REVIEW
Matthew Leibovitch, Ivan Topisirovic
Dysregulated mRNA translation and aberrant energy metabolism are frequent in cancer. Considering that mRNA translation is an energy demanding process, cancer cells must produce sufficient ATP to meet energy demand of hyperactive translational machinery. In recent years, the mammalian/mechanistic target of rapamycin (mTOR) emerged as a central regulatory node which coordinates energy consumption by the translation apparatus and ATP production in mitochondria. Aberrant mTOR signaling underpins the vast majority of cancers whereby increased mTOR activity is thought to be a major determinant of both malignant translatomes and metabolomes...
November 2, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29145888/tgf-%C3%AE-2-initiates-autophagy-via-smad-and-non-smad-pathway-to-promote-glioma-cells-invasion
#12
Chao Zhang, Xin Zhang, Ran Xu, Bin Huang, An-Jing Chen, Chao Li, Jian Wang, Xin-Gang Li
BACKGROUND: Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood...
November 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29144008/a-copper-ii-phenanthroline-metallopeptide-that-targets-and-disrupts-mitochondrial-function-in-breast-cancer-stem-cells
#13
Kristine Laws Laws, Ganka Bineva-Todd, Arvin Eskandari, Chunxin Lu, Nicola O'Reilly, Kogularamanan Suntharalingam
The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides, 1-4 containing dichloro(1,10-phenanthroline) copper(II) and various organelle-targeting peptide sequences, is reported. The mitochondrial-targeting metallopeptide, 1 exploits the higher mitochondrial load in breast CSCs over corresponding non-CSCs, and the vulnerability of breast CSCs to mitochondrial damage, to potently and selectivity kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a better extent than salinomycin, an established CSC-potent agent...
November 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29143843/mitochondria-targetable-carbon-quantum-dots-for-differentiating-cancerous-cells-from-normal-cells
#14
Ge Gao, Yao-Wen Jiang, Jingjing Yang, Fu-Gen Wu
In this study, a series of fluorescent carbon quantum dots (or carbon dots, CDs) with inherent mitochondrial targeting/imaging and cancerous/normal cell differentiation capabilities were prepared by a one-pot solvothermal treatment of glycerol and a silane molecule. Glycerol acted as a solvent and carbon source, and the silane molecule acted as a passivation agent. The as-prepared CDs could specifically and stably (for at least 24 h) visualize mitochondria of various types of cells without the introduction of mitochondria-targeting ligands (such as triphenylphosphonium)...
November 16, 2017: Nanoscale
https://www.readbyqxmd.com/read/29143351/apoptotic-and-antiproliferative-properties-of-3%C3%AE-hydroxy-%C3%AE-5-steroidal-congeners-from-a-partially-purified-column-fraction-of-dendronephthya-gigantea-against-hl-60-and-mcf-7-cancer-cells
#15
I P Shanura Fernando, K K Asanka Sanjeewa, Hyun-Soo Kim, Lei Wang, Won Woo Lee, You-Jin Jeon
Organisms belonging to the genus Dendronephthya are among a group of marine invertebrates that produce a variety of terpenoids with biofunctional properties. Many of these terpenoids have been proven effective as anticancer drugs. Here, we report the antiproliferative effect of 3β-hydroxy-Δ5-steroidal congeners against the proliferation of HL-60 human leukemia cells and MCF-7 human breast cancer cells. The sterol-rich fraction (DGEHF2-1) inhibited the growth of HL-60 and MCF-7 cells with IC50 values of 13...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#16
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29141558/modulation-of-cancer-metabolism-by-phytochemicals-a-brief-overview
#17
Danina Muntean, Sturza Adrian, Ioana Pavel, Oana Duicu
Despite tremendous research efforts for effective therapies, cancer remains the plague of the century and its burden is expected to increase worldwide in the near future. Metabolic reprogramming is a firmly established hallmark of all cancers, regardless their cellular or tissue origin, being a prerequisite for both tumor growth and invasion. Functional dependence of tumors on glycolysis and glutaminolysis and the crucial contribution of mitochondria to the tumor bioenergetic versatility are well recognized features and established therapeutic targets...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29141199/disruption-of-mitochondrial-function-as-mechanism-for-anti-cancer-activity-of-a-novel-mitochondriotropic-menadione-derivative
#18
José Teixeira, Ricardo Amorim, Katia Santos, Pedro Soares, Sandipan Datta, Gino A Cortopassi, Teresa L Serafim, Vilma A Sardão, Jorge Garrido, Fernanda Borges, Paulo J Oliveira
Menadione, also known as vitamin K3, is a 2-methyl-1,4 naphthoquinone with a potent cytotoxic activity mainly resulting from its quinone redox-cycling with production of reactive oxygen species (ROS). Although increased ROS generation is considered a relevant mechanism in cancer cell death, it may not be sufficiently effective to kill cancer cells due to phenotypic adaptations. Therefore, combining ROS-generating agents with other molecules targeting important cancer cell phenotypes can be an effective therapeutic strategy...
November 12, 2017: Toxicology
https://www.readbyqxmd.com/read/29138856/differentially-expressed-proteins-in-the-human-esophageal-cancer-cell-line-eca%C3%A2-109-in-the-presence-and-absence-of-gemcitabine
#19
Zenghuang Ma, Xiaojie Xue
The present study aimed to screen and study the roles of differentially expressed proteins in the human esophageal cancer cell line Eca‑109, in the presence and absence of gemcitabine (GEM). The 3‑(4,5)‑dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method was used to assay the vitality of the Eca‑109 cells following treatment with GEM (1‑16 µg/ml). The cell apoptosis was measured by using fluorescence activated cell sorting. The proteins in the treated Eca‑109 cells were extracted, validated, and assayed via two‑dimensional gel electrophoresis combined with matrix‑assisted laser desorption/ionization time of flight mass spectrometry (MALDI‑TOF‑MS)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138795/hesperidin-induces-apoptosis-and-g0-g1-arrest-in-human-non-small-cell-lung-cancer-a549-cells
#20
Rongmu Xia, Xin Sheng, Xianlin Xu, Chunbo Yu, Hongling Lu
Lung cancer has high incidence and mortality rates worldwide. In the present study, the mechanisms by which hesperidin decreases the viability and induces the apoptosis of human non-small cell lung cancer (NSCLC) A549 cells were investigated. Initially, MTT and flow cytometric assays were performed to evaluate the effects of hesperidin on the viability and apoptosis of A549 cells and human normal lung epithelial BEAS-2B cells. The results revealed that hesperidin has no negative effects on the human normal lung epithelial BEAS-2B cells and the viability of cells treated with various concentrations of hesperidin was inhibited in a time- and dose-dependent manner compared with the control groups...
November 9, 2017: International Journal of Molecular Medicine
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