Cell Cycle Checkpoints

Publication Title: 
Oxidative Medicine and Cellular Longevity

The mechanisms that concern DNA repair have been studied in the last years due to their consequences in cellular homeostasis. The diverse and damaging stimuli that affect DNA integrity, such as changes in the genetic sequence and modifications in gene expression, can disrupt the steady state of the cell and have serious repercussions to pathways that regulate apoptosis, senescence, and cancer. These altered pathways not only modify cellular and organism longevity, but quality of life ("health-span").

Author(s): 
Conde-PÈrezprina, Juan CristÛbal
LeÛn-Galv·n, Miguel ¡ngel
Konigsberg, Mina
Publication Title: 
Cell Cycle (Georgetown, Tex.)

Cellular quiescence is a reversible cell cycle arrest that is poised to re-enter the cell cycle in response to a combination of cell-intrinsic factors and environmental cues. In hematopoietic stem cells, a coordinated balance between quiescence and differentiating proliferation ensures longevity and prevents both genetic damage and stem cell exhaustion. However, little is known about how all these processes are integrated at the molecular level.

Author(s): 
Yamada, Takeshi
Park, Chun Shik
Lacorazza, H. Daniel
Publication Title: 
Advances in Experimental Medicine and Biology

The growth arrest and DNA damage-inducible (Gadd)45 proteins have been associated with numerous cellular mechanisms including cell-cycle control, DNA damage sensation and repair, genotoxic stress, neoplasia, and molecular epigenetics. The genes were originally identified in in vitro screens of irradiation- and interleukin-induced transcription and have since been implicated in a host of normal and aberrant central nervous system processes. These include early and postnatal development, injury, cancer, memory, aging, and neurodegenerative and psychiatric disease states.

Author(s): 
Sultan, Faraz A.
Sweatt, J. David
Publication Title: 
Epigenetics

Epigenetic proteins have recently emerged as novel anticancer targets. Among these, bromodomain and extra terminal domain (BET) proteins recognize lysine-acetylated histones, thereby regulating gene expression. Newly described small molecules that inhibit BET proteins BRD2, BRD3, and BRD4 reduce proliferation of NUT (nuclear protein in testis)-midline carcinoma, multiple myeloma, and leukemia cells in vitro and in vivo. These findings prompted us to determine whether BET proteins may be therapeutic targets in the most common primary adult brain tumor, glioblastoma (GBM).

Author(s): 
Pastori, Chiara
Daniel, Mark
Penas, Clara
Volmar, Claude-Henry
Johnstone, Andrea L.
Brothers, Shaun P.
Graham, Regina M.
Allen, Bryce
Sarkaria, Jann N.
Komotar, Ricardo J.
Wahlestedt, Claes
Ayad, Nagi G.
Publication Title: 
Antimicrobial Agents and Chemotherapy

The declining efficacy of artemisinin derivatives against Plasmodium falciparum in western Cambodia is a major concern. The knowledge gap in the understanding of the mechanisms involved hampers designing monitoring tools. Here, we culture-adapted 20 isolates from Pailin and Ratanakiri (areas of artemisinin resistance and susceptibility in western and eastern Cambodia, respectively) and studied their in vitro response to dihydroartemisinin. No significant difference between the two sets of isolates was observed in the classical isotopic test.

Author(s): 
Witkowski, Benoit
Khim, Nimol
Chim, Pheaktra
Kim, Saorin
Ke, Sopheakvatey
Kloeung, Nimol
Chy, Sophy
Duong, Socheat
Leang, Rithea
Ringwald, Pascal
Dondorp, Arjen M.
Tripura, Rupam
Benoit-Vical, Françoise
Berry, Antoine
Gorgette, Olivier
Ariey, Frédéric
Barale, Jean-Christophe
Mercereau-Puijalon, Odile
Ménard, Didier
Publication Title: 
Antimicrobial Agents and Chemotherapy

Drug-resistant Plasmodium falciparum malaria is a major public health problem. An elevated pfmdr1 gene copy number (CN) is known to decrease parasite sensitivity to the commonly used antimalarial mefloquine (MFQ). To understand the relationship between pfmdr1 CN and mefloquine resistance, we evaluated pfmdr1 transcript levels in three P. falciparum strains with different CNs in the presence and absence of MFQ.

Author(s): 
Bohórquez, Elaine B.
Juliano, Jonathan J.
Kim, Hyung-Suk
Meshnick, Steven R.
Publication Title: 
PloS One

This report is designed to explore the molecular mechanism by which dihydroartemisinin (DHA) and ionizing radiation (IR) induce apoptosis in human lung adenocarcinoma A549 cells. DHA treatment induced a concentration- and time-dependent reactive oxygen species (ROS)-mediated cell death with typical apoptotic characteristics such as breakdown of mitochondrial membrane potential (??m), caspases activation, DNA fragmentation and phosphatidylserine (PS) externalization.

Author(s): 
Chen, Tongsheng
Chen, Min
Chen, Jingqin
Publication Title: 
Toxicology

Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate.

Author(s): 
Kössler, Sonja
Nofziger, Charity
Jakab, Martin
Dossena, Silvia
Paulmichl, Markus
Publication Title: 
BMC complementary and alternative medicine

BACKGROUND: Inhibition of the proteolytic activity of 26S proteasome, the protein-degrading machine, is now considered a novel and promising approach for cancer therapy. Interestingly, proteasome inhibitors have been demonstrated to selectively kill cancer cells and also enhance the sensitivity of tumor cells to chemotherapeutic agents. Recently, polyphenols/flavonoids have been reported to inhibit proteasome activity. Murraya koenigii Spreng, a medicinally important herb of Indian origin, has been used for centuries in the Ayurvedic system of medicine.

Author(s): 
Noolu, Bindu
Ajumeera, Rajanna
Chauhan, Anitha
Nagalla, Balakrishna
Manchala, Raghunath
Ismail, Ayesha
Publication Title: 
Aging

Berberine (BRB), a natural alkaloid, has a long history of medicinal use in both Ayurvedic and old Chinese medicine. Recently, available as a dietary supplement, Berberine is reported to have application in treatment of variety diseases. Previously we observed that BRB inhibited mTOR/S6 signaling concurrently with reduction of the level of endogenous oxidants and constitutive DNA damage response. We currently tested whether Berberine can affect premature, stress-induced cellular senescence caused by mitoxantrone.

Author(s): 
Zhao, Hong
Halicka, H. Dorota
Li, Jiangwei
Darzynkiewicz, Zbigniew

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