Jinxiang Zhang

Shiwei Deng

Si Jin

Xiao Qian Chen

Yongzhong Wu

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Editorial
Oxidants and Antioxidants in Metabolic Syndrome and Cancer
Si Jin,1 Yongzhong Wu,2 Shiwei Deng,3 Jinxiang Zhang,4 and Xiao Qian Chen5
1 Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
2 Laboratory of Molecular Pharmacology, Oxidative Signaling and Molecular Therapeutics Section, Center for Cancer Research,
National Cancer Institute, Bethesda, MD 20892, USA
3Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Obere Zahlbacher Straße 67,
55131 Mainz, Germany
4Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan 430022, China
5 Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Correspondence should be addressed to Si Jin; jinsi@mails.tjmu.edu.cn
Received 25 May 2014; Accepted 25 May 2014; Published 24 June 2014
Copyright © 2014 Si Jin et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Metabolic syndrome, which includes hypertension, hyper-
lipidemia, obesity, insulin resistance or glucose intolerance,
and fatty liver diseases, significantly contributes to the
increased risk of cardio- or cerebral-vascular diseases and
diabetes [1]. Cancer represents a group of malignantly prolif-
erative diseases. Recently, metabolic reprogramming changes
were extremely highlighted in cancer cells, putting forward
to a trend that cancer should also be treated as a type of
metabolic disease [2]. As a matter of fact, statins, the most
prescribed low density lipoprotein (LDL) lowering agents,
and metformin, the most prescribed antidiabetic drug, have
both been reported to associate with decreased cancer risk
[3, 4].
Meanwhile, in the past decade, a growing body of
evidence has implicated that increased oxidative stress is a
common and key feature of metabolic diseases [5]. Whereas
a recent hypothesis paper byWatson, the famous Nobel Prize
winner, suggests that diabetes, dementias, cardiovascular
disease, and some cancers may be linked to a failure to
generate sufficient reactive oxygen species (ROS) [6], which
maybe reflects the situations in end stages of these complex
diseases. ROS play very important roles in carcinogenesis
and the maintenance of cancer cells. The ROS levels are
reported to be very high in cancer cells, which drive the high
rate of proliferation in these malignant cells [7]. Whether
prooxidants or antioxidants could be used to treat cancer or
not remains elusive.
In this controversial context, we organized this special
issue.
Although insulin is critically involved in metabolism
regulation and closely associates with both diabetes and
cancer, the precise molecular mechanism is not fully elu-
cidated. In this special issue, Q. Li et al. conducted an
interesting study, which demonstrates that insulin increases
pyruvate kinase M2 (PKM2) expression through ROS for the
regulation of glucose consumption and lactate production
“Insulin regulates glucose consumption and lactate production
through reactive oxygen species and pyruvate kinase M2”. J.
Zhao et al. demonstrated that pubertal obesity was associated
with increased oxidative stress in testis tissue and high levels
of leptin, which maybe the cause of male hypogonadism
in obesity “Leptin level and oxidative stress contribute to
obesity-induced low testosterone in murine testicular tissue.”
Oxidized low density lipoprotein (oxLDL) is the major lipid
found in atherosclerotic lesion and elevated plasma oxLDL
is recognized to be a risk factor of atherosclerosis. W. Li
et al. in this special issue emphasized the critical role of
oxLDL transcytosis across endothelial cells in the initiation of
atherosclerosis, providing novel insight into the pathogenesis
of this complex metabolism disease “Endogenous ceramide
contributes to the transcytosis of oxLDL across endothelial
cells and promotes its subendothelial retention in vascular
wall.” For the therapy of metabolic syndrome-related dis-
orders, J. Wang et al. reported in this special issue that
Hindawi Publishing Corporation
Oxidative Medicine and Cellular Longevity
Volume 2014, Article ID 178962, 3 pages
http://dx.doi.org/10.1155/2014/178962
2 Oxidative Medicine and Cellular Longevity
amagnolia extract, named BL153, could prevent obesity-
induced liver damage via inhibition of lipid accumulation,
inflammation, oxidative stress “BL153 partially prevents high
fat diet induced liver damage probably via inhibition of lipid
accumulation, inflammation, and oxidative stress.” Centella
asiatica is a traditional Chinese medicine which has been
reported to have antioxidant effect in vitro. In this special
issue, Y. Zhao et al. further reported that Centella asiatica
decreased cholesterol and triglyceride in mice model “Effect
of Centella asiatica on oxidative stress and lipid metabolism in
hyperlipidemic animal models.” Salidroside (SAL) is an active
component ofRhodiola Roseawith documented antioxidative
properties. S. Xing et al. in this issue further demonstrated
that SAL could protect endothelium against H
2
O
2
-induced
injury via promoting mitochondrial biogenesis and func-
tion, thus preventing the over-activation of oxidative stress-
related downstream signaling pathways “Salidroside stim-
ulates mitochondrial biogenesis and protects against H2O2-
Induced endothelial dysfunction.”
In cancer cells, the ROS is maintained at higher levels
than normal cells and mainly exerts its proliferative actions.
When ROS levels are further increased by prooxidants so
as to exceed a border line level, the proapoptotic effects
of ROS may exceed its proliferative effects and cytotoxic
effects display in cancer cells, whereas the ROS levels in
normal cells remain below the border line level which is
nontoxic to normal cells. In consistent with this view, several
studies in this special issue reported chemicals could kill
cancer cells by inducing ROS accumulation as cancer killing
agents. Piperlongumine (PL) is a natural alkaloid from Piper
longumL., possessing highly selective and effective anticancer
property. L.-H. Gong et al. reported in this special issue
that PL notably induced cell apoptosis, G2/M phase arrest
and intracellular ROS accumulation in a dose- and time-
dependent manner. Pretreatment with antioxidant N–acety-
L-cysteine could reverse the PL-induced ROS accumulation
and cellular apoptosis. In addition, low-dose of PL/cisplatin
or paclitaxel combination therapies had a synergistic anti-
growth effect on human ovarian cancer cells “Piperlongumine
induces apoptosis and synergizes with cisplatin or paclitaxel in
human ovarian cancer cells.” Q. R. Liu et al. also reported
that Piperlongumine effectively inhibited the migration of
human glioma cells but not normal astrocytes in the scratch-
wound culturemodel. PL increasedROSproduction, reduced
glutathione, activated p38 and JNK pathway, increased I𝜅B
and suppressed NF-𝜅B in LN229 cells after scratching
“Piperlongumine inhibits migration of glioblastoma cells via
activation of ROS-dependent p38 and JNK signaling pathways”.
Similarly, H. Li et al. also reported in this issue that Lithium
chloride, the established glycogen synthase kinase-3𝛽 (GSK-
3𝛽) inhibitor, induced the apoptosis of colorectal cancer
cells by induction of ROS signaling “Lithium chloride sup-
presses colorectal cancer cell survival and proliferation through
ROS/GSK-3𝛽/NF-𝜅B signaling pathway.”
In contrast to above observations which demonstrate that
induction of ROS may be used to treat cancers, Y-Q. Xue et
al., in this special issue reviews the preventive or anticancer
properties of resveratrol oligomers. Resveratrol is a naturally
derived phytoalexin stilbene isolated from grapes and other
plants with documented antioxidant activity “Resveratrol
oligomers for the prevention and treatment of cancers.” In
line with this review, Y. Li et al. reported that NADPH
oxidase 4 (Nox4)-derived reactive oxygen species might play
crucial roles in the invasion, angiogenesis and radioresis-
tance in glioblastoma. Inhibition of Nox4 by lentivirus-
mediated small hairpin interfering RNA (shRNA) could be
a strategy to overcome radioresistance and in turn improve
the therapeutic efficacy “Lentivirus-mediated Nox4 shRNA
invasion and angiogenesis and enhances radiosensitivity in
human glioblastoma.” These studies suggest that in addition
to prooxidant therapy, antioxidants may also be the right
option to treat cancers as cancer inhibiting agents.
In addition to above mentioned pathological or phar-
macological studies, Elizabeth Moreno-Arriola et al. present
an interesting review which suggests that Caenorhabditis
elegans, which may be one of the most famous model organ-
isms, is also a suitable disease model reflecting the oxidative
status in metabolic disorders, providing new approaches for
studying metabolic diseases “Caenorhabditis elegans: a useful
model for studyingmetabolic disorders in which oxidative stress
is a contributing factor.”
From these collected studies in this special issue, we
appear to come to the consensus that upregulated oxidative
stress indeed promotes the development of both metabolic
syndrome and cancer. Antioxidants are suitable choices for
the prevention or treatment of metabolic syndrome-based
cardiovascular diseases or diabetic mellitus, which are also
classified as chronic nonresolving inflammatory diseases [8].
However, for the treatment of cancers, both prooxidants and
antioxidants might work via different mechanisms, provided
that the drug selectivity on targeted tissue is guaranteed. We
hope that the studies and discussions gathered in this issue
reflect the current trend in this area and could, to some
extent, stimulate more in-depth studies in this somehow
controversial field.
Acknowledgments
We appreciate the great efforts of all authors and reviewers
participating in this issue. Without their invaluable contribu-
tion, this special issue would not be a success.
Si Jin
Yongzhong Wu
Shiwei Deng
Jinxiang Zhang
Xiao Qian Chen
References
[1] I. Padmalayam and M. Suto, “Role of adiponectin in the
metabolic syndrome: current perspectives on its modulation as
a treatment strategy,”Current Pharmaceutical Design, vol. 19, no.
32, pp. 5755–5763, 2013.
[2] C. V. Dang, “Links between metabolism and cancer,” Genes &
Development, vol. 26, no. 9, pp. 877–890, 2012.
[3] B. J. Quinn, H. Kitagawa, R. M. Memmott, J. J. Gills, and P. A.
Dennis, “Repositioning metformin for cancer prevention and
Oxidative Medicine and Cellular Longevity 3
treatment,” Trends in Endocrinology & Metabolism, vol. 24, no.
9, pp. 469–480, 2013.
[4] S. F. Nielsen, B. G. Nordestgaard, and S. E. Bojesen, “Statin use
and reduced cancer-relatedmortality,”TheNewEngland Journal
of Medicine, vol. 367, no. 19, pp. 1792–1802, 2012.
[5] C. K. Roberts and K. K. Sindhu, “Oxidative stress andmetabolic
syndrome,” Life Sciences, vol. 84, no. 21-22, pp. 705–712, 2009.
[6] J. D. Watson, “Type 2 diabetes as a redox disease,” The Lancet,
vol. 383, no. 9919, pp. 841–843, 2014.
[7] C. Gorrini, I. S. Harris, and T. W. Mark, “Modulation of
oxidative stress as an anticancer strategy,” Nature Reviews Drug
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Editorial Oxidants and Antioxidants in Metabolic Syndrome and Cancer

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Editorial Oxidants and Antioxidants in Metabolic Syndrome and Cancer

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