Short Communication
Eating Right to Block Left Premalignant Lesion of GI Cancers
Yong Seok Kim1, Jong Min Park2, Young Min Han2, Ji Young Oh3, Shin A Shin2 and Ki Baik Hahm2,4*
11Department of Biochemistry and Molecular Biology, Hanyang University College of Medicine, Korea
2Department of Biochemistry and Molecular Biology, CHA Cancer Prevention Research Center, Korea
3Department of Biochemistry and Molecular Biology, CJ Food Research Institute, Korea
4Digestive Disease Center, CHA University Bundang Medical Center, Korea
*Corresponding author: Ki Baik Hahm, Department of Biochemistry and Molecular Biology, CHA University Bundang Medical Center, Korea
Published: 20 Mar, 2017
Cite this article as: Kim YS, Park JM, Han YM, Oh JY, Shin
SA, Hahm KB. Eating Right to Block
Left Premalignant Lesion of GI Cancers.
Clin Oncol. 2017; 2: 1227.
Short Communication
Cancer prevention, chemoprevention, cancer delay, and chemoquiescence
Prof. WK Hong and prof. MB Sporn in their publication at "Science" journal [1] defined
chemoprevention as cancer prevention using pharmacologic or natural agents that inhibit the
development of invasive cancer either by blocking the DNA damage or by reversing the progression
of premalignant cells. Their efforts to achieve “chemoprevention” were highlighted more because
that though "war on cancer" was declared by President Richard Nixon in 1971, cancer statistics
from the American Cancer Society and other sources suggested the failure of this war, leaving
strong message that a "prevention strategy" might be much better than drastic war on cancer
[2]. Recently, increasing emergence of Cancer Stem Cell (CSC) researches led to the feasibility of
removing Tumor Initiating Cells (TICs), metastasis initiating cells, and underlying CSCs, after
which the concept “chemo quiescence” is also stressed in oncology as ultimate purpose of cancer
cure. With the advancement of molecular targeted therapeutics or non-invasive removal of cancer
such as endoscopic treatment [3], the studies regarding molecular targeted prevention of cancer is
increasingly achieved and with scientific achievements telling that chronic inflammation is one of core
hallmarks in carcinogenesis, several strategies had been applied and studied that anti-inflammatory
intervention can be faithful strategy to prevent cancer [4]. Especially in Gastrointestinal (GI) tract,
the prevention of Barrett’ esophagus, Helicobacter pylori (H. pylori)-associated Chronic Atrophic
Gastritis (CAG) with intestinal metaplasia, and long-term inflammatory bowel diseases can be
possible with the introduction of either synthetic or natural agents [5]. In detail, the major barrier
to more successful cancer immunotherapy is the Tumor Microenvironment (TME), where chronic
inflammation played a predominant role in carcinogenesis, cancer cell proliferation, angiogenesis,
and immunosuppression. Increasing understanding of cancer-related inflammation has significantly
advanced to inhibition of inflammatory mediators or their signaling molecules, blocking of myeloid
cells recruitment, and modulation of immunosuppressive functions, and re-education of TME [6].
In this short communication, we have introduced, among novel approaches for GI cancers with
proton pump inhibitor, smad7 anti-sense oligonucleotide, non-steroidal anti-inflammatory drug,
autophagy regulator, natural or dietary agents in correcting TME under the theme that eating right
can be right way for cancer prevention.
siTRP (short-term intervention to revert premalignant lesions) strategy as part of
chemoprevention
The continuing magnitude and burdening of the cancer problem make it imperative to develop
an innovative preventive approach to this disease. In detail, as advances in the molecular and
cellular biology of carcinogenesis continue, specific targets for preventive intervention are being
profusely identified, and higher effective chemo preventive agents are being synthesized and tested
[7]. As much as the developments of molecular targeted therapeutics and creation of synthetic
lethality concept, in the near future, molecular targeted cancer prevention will be come true for
cancer conquest. Especially, further understanding of inflammatory mediators and cancer stem cell
biology, rejuvenation of chronic degenerative diseases as well as chemo quiescence will be tried
before irreversible change of carcinogenesis. Our group nominated these strategies as siTRP. Results
from our laboratory strongly suggested the high possibility of reverting premalignant lesions into
non-tumorous condition through short-term effective intervention. Inflammation-based GI tract diseases, including reflux esophagitis, H. pylori-associated gastritis,
non-steroidal anti-inflammatory drug-induced enteritis, ulcerative
colitis, and associated colorectal cancer, are ultimate target [8].
Eating right to prevent cancer through reverting
premalignant lesions
Though recent advances in cancer immunotherapy, for example,
immune checkpoint blockade therapy, have dramatically changed
the therapeutic strategy against advanced malignancies, the unmet
medical need in cancer immunotherapy is that only a subset of
patients shows a good response [9]. Therefore, the efforts to correct
TME are still prerequisite and nutrients or natural products can
contribute greatly to this concern correcting TME. In order to
achieve this, eating right seems to be answer and the strategy to
leave premalignant lesions as it is seems to be potential way. Some
examples will be introduced in this communication.
Artemisia and green tea extracts: Since the discovery of H.
pylori infection as the major cause of gastro duodenal disorders
including acute and chronic gastritis, gastro duodenal ulcer, CAG,
and gastric cancer almost three decades ago, the possibility of
preventing these clinical diseases through eradicating H. pylori has
been the focus of active research. Our group set strong hypothesis
that non-microbial, dietary approach might be the alternate, for
which several interventions of nutritional components can aim
rejuvenation of CAG [10]. The experience and outcome regarding
nutritional application to rejuvenate gastric atrophy was reported
with the following natural agents including Artemisia and green tea
extract, Korean red ginseng, garlic extracts, cancer preventive kimchi,
n-3 Polyunsaturated Fatty Acids (PUFA), special form of licorice,
and probiotics. Among these, we evaluated the efficacy of long-term
dietary administration of Artemisia and green tea extracts on H. pyloriinitiated,
high-salt-promoted chronic atrophic gastritis and gastric
tumorigenesis mouse model [11]. As reported, the erythematous and
nodular changes and mucosal ulcerative and erosive lesions were
noted in the control group at 24 weeks, while Artemisia and green tea
extracts showed significantly ameliorated pathologic lesion compared
to the control group. After the 36 weeks, scattered nodular masses
with some central ulcers and thin gastric surface were noted in the
control stomach, whereas no tumorous lesion and milder atrophic
changes were observed in Artemisia and green tea extracts groups.
On molecular analysis, increased expressions of COX-2, TNF-α,
IL-6, lipid peroxide, and activated STAT3 relevant to H. pylori
infection were significantly decreased with Artemisia and green tea
extracts administration (p <0.01), whereas HSP70 was significantly
increased. 15-PGDH expressions, core tumor suppressor involved in
carcinogenesis, were significantly decreased with H. pylori infection
(p <0.05), but significantly increased in Artemisia and green tea
extract group (p <0.05). Conclusively, long-term dietary intake of
Artemisia and green tea extracts can be an effective strategy either to
rejuvenate H. pylori atrophic gastritis or to suppress tumorigenesis.
Cancer preventive kimchi (cpkimchi) for GI cancer: Our group
developed cpkimchi and administered to chronic H. pylori-initiated,
high salt diet-promoted, gastric tumorigenesis mice model. As
results, the erythematous and nodular changes, mucosal ulcerative
and erosive lesions noted in the stomach of 24 weeks wild type mice
were significantly ameliorated with cpkimchi administration. After
36 weeks, scattered nodular masses, some ulcers, and thin nodular
gastric mucosa were noted in H. pylori-infected wild type mice, but
these gross lesions were significantly attenuated in cpkimchi group.
On molecular analysis, significant expressions of COX-2 and IL-
6, activated NF-κB and STAT3, increased apoptosis, and marked
oxidative stresses were noted in H. pylori-infected WT group, but
these were all significantly attenuated in cpkimchi group. With
interest, cpkimchi extracts afforded significant selective induction
of apoptosis only in cancer cells, led to inhibition of H. pyloriinduced
proliferation, while no cytotoxicity through significant
HO-1 induction in non-transformed gastric cells. Conclusively, daily
dietary intake of cpkimchi can be an effective way either to rejuvenate
H. pylori-atrophic gastritis or to prevent tumorigenesis supported
with the concerted actions of anti-oxidative, anti-inflammatory, and
anti-mutagenic mechanisms [12].
ω-3 PUFAs: Using Fat-1 transgenic mice, which can synthesize
ω-3 PUFAs due to presence of 6-desaturase, we compared the
serial gastric pathologies after H. pylori infection. As results, Fat-1
TG mice showed significantly attenuated gastritis as well as gastric
tumorigenesis compared to wild type littermates, signifying that longterm
intake of ω-3 PUFAs can provide protection from H. pyloriassociated
CAG and gastric cancer [13]. Though general eradication
in patients with chronic gastritis was intervened in Japan as drastic
effort to decrease H. pylori-associated gastric cancer, non-microbial
and nutritional intervention can be an alternate to these costexpensive
and skewed strategies can be preferred [10]. Conclusively,
we recommend that eating right to prevent left premalignant lesions.
References
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- Jeong M, Park JM, Han YM, Kangwan N, Kwon SO, Kim BN, et al. Dietary intervention of Artemisiaand green tea extracts to rejuvenate Helicobacter pylori-associated chronic atrophic gastritis and to prevent tumorigenesis. Helicobacter. 2016; 21: 40-59.
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