Research Article: Effect of ethyl acetate extract of usnea longissima on esophagogastric adenocarcinoma in rats1

Date Published: March 18, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em

Author(s): Renad Mammadov, Bahadir Suleyman, Durdu Altuner, Elif Demirci, Nihal Cetin, Adnan Yilmaz, Huseyin Baykal, Hilal Alpcan, Emine Akyuz Turumtay, Halis Suleyman.


To investigate the effects of the EtOAc extract of U.
longissima which is uninvestigated previously on
esophagogastric cancer induced in rats with
N-methyl-N-nitro-N-nitrosoguanidin (MNNG).

The anticancer activity of EtOAc extract of U. longissima
was examined in the esophagogastric adenocarcinoma models induced in rats
with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg
oral doses were administered once daily for six months. MNNG induced
differentiated and undifferentiated type adenocarcinomas in the esophageal
and gastric tissues of rats.

EtOAc extract of U. longissima obtained from U.
longissima prevented gastric and esophageal cancerogenesis
induced in rats with MNNG. EtOAc extract of U. longissima
did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The
prominent anticarcinogenic activity of EtOAc extract of U.
longissima 50 and 100 mg/kg suggests that it is not toxic and
it is selective to the cancer tissue.

This information may shed light on clinical implementation of EtOAc extract
of U. longissima in future.

Partial Text

In the treatment of cancer, different methods are used to reduce mortality and
morbidity; such as surgery, radiotherapy, chemotherapy, immunotherapy, signal
transduction inhibitors, gene therapy and angiogenesis inhibitors1. However, according to the recent statistics, more than 8 million people die
from cancer every year2. This shows that modern medicine lacks effective curative options for the
treatment of cancer patients. The current drug therapy does not produce the desired
response due to the doses having a toxic effect not only on cancer cells but also on
healthy cells3. For cancer treatment to be successful, substances that only have a toxic
effect on cancer cells are needed. Therefore, there is increasing amount of global
efforts to produce synthetic, herbal and fungal drugs to treat various types of
cancer4,5. Research suggests that lichens and their metabolites can be used as an
alternative method for treating cancer3. Lichens are not a single organism; they are symbiotic, composite organisms
composed of fungi (ascomycetes, basidiomycetes) and photosynthetic algae6. In this lichen structure, algae and fungi act as single individuals;
however, in symbiosis they can produce chemicals that they cannot produce alone.
Some of the thousands of secondary metabolites produced by lichens are fulvic,
protolichesterinic, fusidic, lobaric, fumarprotocetraric and usnic acids, as well as
depsides and depsidons7. In this study, the anticarcinogenic activity of a lichen type acid, usnea
longissima, was investigated. Although lichens have a medical value due to their
antibiotic, antifungal, antiviral and anticarcinogenic properties, only a few of the
several types have been researched and reported to exhibit anticarcinogenic
activity8,9. A common problem related to natural drugs is the lack of information about
their pharmacologic activities and active components4. The anticarcinogenic activities of these chemicals can be investigated
through in vivo and in vitro experiments10. The commonly used in vivo models involve the induction of gastric and
esophageal cancer by MNNG11. The literature contains research on the effect of the extracts of different
lichen types on gastric and esophageal cancer induced by MNNG. In this study, we
investigated the effects of an ethyl acetate (EtOAc) extract of U.
longissima on esophagogastric cancer (adenocarcinoma) induced by MNNG
in rats. The reason for using ethyl acetate extract was found to be more effective
than other extracts (water extract, ethanol extract, methanol extract) in cell
cultures. However, ethyl acetate are mostly suitable for diffractaic acid, usnic
acid and evernic acid wich were the majör compounds of U.

The study was approved by the university Local Ethical Committee on Animal
Experimentation (dated March 3, 2014 and numbered 2014/19).

This study investigated the effect of EtOAc on the esophagogastric adenocarcinoma
induced in rats by MNNG. The results of the experiment showed the formation of
carcinoma and undifferentiated tumor sites in the esophagogastric tissue of the rats
in the EC group. As described in the methodology section, the esophagogastric cancer
model was induced by an oral injection of MNNG. The review of the literature shows
that MNNG is used in different doses and for different durations to develop a cancer
model. For example, Wang et al.18 reported that they induced gastrointestinal cancer in rats mixing MNNG with
their drinking water for 24 weeks. In an earlier study, we used a similar dose of
MNNG over a similar period to induce cancer in rats15. Sugano et al.19 classified gastric gastric carcinoma into two main groups as differentiated
(papillary and tubular adenocarcinoma) and undifferentiated (poorly differentiated
signet-ring cell carcinoma). The pathological findings from previous reports and
observed in the current study show that we developed an appropriate cancer model to
investigate the effects of the chemical of interest on gastric and esophageal

The EtOAc extract of U.longissima has anticancer activity. EtOAc extract of
U.Longissima was found to have no toxic effect. These results
indicate that EtOAc extract of U.Longissima shows selectivity to cancerous tissue. In addition,
EtOAc extract of U.Longissima is thought to be a therapeutic agent against the
formation of esophageal and gastric adenocarcinoma. This results of the study may
lead to clinical use of EtOAc extract of U. Longissima in the




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