2010; Volume 1; Issue 1 (January -April)
Editorial: Good news: the Journal of Theoretical and Experimental Pharmacology was born
J Theor Exp Pharmacol 2010; 1 (1): 1-2

Alejandro A. NAVA-OCAMPO(a,b)
(a)Department of Pharmacology & Toxicology, Faculty of Medicine, University of Toronto, Toronto, Canada
(b)PharmaReasons, Toronto, Canada
Correspondence: editor.jtep@premiumreasons.com
REVIEW ARTICLE: Mitochondria as a target for novel chemotheraputic agents based on phenolic acids
J Theor Exp Pharmacol 2010; 1 (1): 3-13

Teresa L. SERAFIM(a), Maria P. MARQUES(b), Fernanda M. BORGES(b,c), Paulo J. OLIVEIRA(a,*)
(a)Center for Neurosciences and Cell Biology, Department of Zoology, and (b)Research Unit ‘Química-
Física Molecular’, University of Coimbra; and (c)Organic Chemistry Department, Pharmacy School,
University of Porto, Portugal
*Corresponding author: pauloliv@ci.uc.pt

molecules lack cell-type specificity, and are unable to kill tumor cells any more efficiently than normal
cells. Also, a high number of those molecules are very toxic. In order to design more effective
chemotherapeutic drugs, it is important to understand the interaction between novel molecules and
biological systems. Certain cellular components are particularly relevant in the context of specific
targeting and mechanisms of action. Mitochondria are not only the major source of cell energy but are also
important in the control of processes that culminate in apoptotic cell death. Particular aspects of
mitochondrial physiology (e.g. the negative transmembrane electric potential) facilitate selective targeting
by anti-cancer molecules. Such mitochondria-specific drugs are referred to as ‘mitocans’. Among
potential mitocans, phenolic acids are attractive candidates. Plant-derived phenolic compounds are
widely consumed in a normal diet, especially in fruits and vegetables. Besides their antioxidant
properties, phenolic acids have been reported to display antiproliferative activity by promoting selective
induction of tumor cell apoptosis. In some cases, the molecule acts by triggering the mitochondrial
pathway for apoptosis. Here we review the potential role of several phenolic acids and derivatives as anti-
cancer agents, highlighting the role of mitochondria as a primary subcellular target for this class of
compounds. The present review intends to raise awareness for this promising direction of research.
REVIEW ARTICLE: Beyond single nucleotide polymorphism
J Theor Exp Pharmacol 2010; 1 (1): 14-20

Roberto CANAPARO* & Loredana SERPE
Department of Anatomy, Pharmacology and Forensic Medicine, Division of Pharmacology and
Experimental Therapeutics, University of Torino, Torino, Italy
*Corresponding author:  roberto.canaparo@unito.it

Similar medications have been known to cause considerable heterogeneity in efficacy and toxicity across
human populations. Therefore, individualized, or personalized, therapy has been highlighted as a
declared goal of modern medicine. In this paper, we briefly describe the main strategies for dose
individualization and then focus our attention on Single Nucleotide Polymorphisms (SNPs), the main
source of human genetic and phenotypic variation. This genetic variation was long recognized as the
principal genetic contribution to the variability of drug action, but the advent of more powerful molecular
technologies has uncovered other abundant DNA variations and changed this perception. It should also
be taken in consideration that most drug effects are determined by the interplay of several genes (the
genomic approach), rather than candidate gene approaches. Although pharmacogenetics and
pharmacogenomics mainly focus on human genetic variations linked to SNPs, we believe that this
approach is only a starting point, from which it will be necessary to proceed to a more complex stage of
research to better individualize drug therapy.
ORIGINAL RESEARCH: Perinatal outcomes to uterine stimulation with breast massage alone or
combination with oxytocin in dystocic sows
J Theor Exp Pharmacol 2010; 1 (1): 21-26

Miguel GONZÁLEZ-LOZANO(a), Daniel MOTA-ROJAS(b,*), Alejandro A. NAVA-OCAMPO(c,d), María
(a)Postgraduate Div. of Animal Science and Health, School of Veterinary and Animal Production, UNAM,
México DF, México, (b)Dept. of Animal Production & Agriculture, Research Area: Ecodesarrollo de la
Producción Animal, UAM-Xochimilco, México DF, México, (c)Department of Pharmacology & Toxicology,
Faculty of Medicine, University of Toronto, Toronto, Canada, (d)PharmaReasons, Toronto, Canada, (e)
Department of Experimental Research & Animal Resources, Instituto Nacional de Ciencias Médicas y  
Nutrición ‘Salvador Zubirán’, and (f)Department of Animal Medicine and Production: Swine, School of
Veterinary and Animal Production, UNAM, México DF, México.
*Corresponding author: dmota100@yahoo.com.mx

Our goal was to evaluate the obstetric and fetal outcomes in dystocic sows receiving udder
massage stimulation alone or in combination with oxytocin.
Methods: 120 sows with maternal or fetal
dystocia were randomly allocated to receive either intravulvar (I-Vu) saline (control group), udder
massage followed by I-Vu saline, or udder massage followed by I-Vu oxytocin 10 IU (groups 1, 2 and 3,
respectively). Udder massage consisted in the application of natural oil while rubbing the udder in a
cephalic-to-caudal direction. Obstetric and fetal outcomes were obtained and compared among the three
groups. The statistically significant limit was fixed to a two-tailed P < 0.05 in every test.
Intensity  of uterine contractions decreased from 18.1 ± 3.6 mmHg in the control group to 14.1 ± 3.8
mmHg (P < 0.001) in group 2. Compared to the control group, there was an approximately 3.3-fold
reduction in the number of moderate-to-severe meconium stained live-born piglets and 50% reduction of
intrapartum deaths in group 2. In group 3, the reduction in these two outcomes was less evident but
remained statistically significant.
Conclusions: Dystocic sows that received udder massage had better
obstetric and fetal outcomes than control sows. However, co-administration of oxytocin might reverse the
advantages of udder massage.
ORIGINAL RESEARCH: Differential effects of histone deacetylase inhibitors on cell cycle regulation
and apoptosis in human prostate cancer cells
J Theor Exp Pharmacol 2010; 1 (1): 27-36

Hee Jin KIM(a), Wahn Soo CHOI(b), Jaewon LEE(a), Jung Yeol HAN(c), Hyung Sik KIM(a,*)
(a)College of Pharmacy, Pusan National University, Busan, South Korea; (b)Department of Immunology,
College of Medicine, Konkuk University, Chungju-Si, South Korea; (c)The Korean Motherisk Program,
Cheil Hospital & Women's Health-care Center, Kwandong University School of Medicine, Seoul, Korea
*Corresponding author: hkims@pusan.ac.kr

Histone deacetylase (HDAC) inhibitors may suppress the proliferation of cancer cells and
induce apoptosis. This study examined the molecular mechanism of how HDAC inhibitors modulate the
cell cycle regulators and tumor suppressor genes in prostate cancer cells.
Methods: HDAC inhibitors
were evaluated according to the following parameters and techniques: (1) cell viability determined by a
microculture tetrazolium assay (MTA); (2) induction of apoptosis according to 4’-6-diamidine-2’-
phenylindole dihydrochloride (DAPI) staining; (3) the expression of cell cycle related proteins such as
CDK2, CDK4, cyclin D1, and cyclin E by Western blot analysis; (4) p16 mRNA expression by RT-PCR; (5)
the acetylation of the histone protein by nuclear protein extraction; and (6) cell cycle analysis by flow
Results: The HDAC inhibitors decreased the level of cell proliferation and induced apoptosis
in human prostate cancer cell lines. Trichostatin A (TSA) caused a significant decrease in cyclin D1/CDK4
expression in LNCaP cells. Cell cycle analysis showed that the TSA treatment increased the proportion of
LNCaP cells in the G1 phase and decreased the proportion of cells in the S phase. The TSA treatment
resulted in the induction of apoptotic cell death which was confirmed by DAPI staining.
TSA increased the level of p16 and WT1 expression in the androgen-dependent LNCaP or androgen-
independent PC3 and DU145 cells.
Conclusions: HDAC inhibitors may prevent the proliferation of
prostate cancer cells by altering the expression of the cell cycle regulators and tumor suppressor genes,
which might be associated with epigenetic regulation.
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