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Journal of Medical Oncology and Therapeutics | Volume: 3
July 23-25, 2018 | Moscow, Russia
12th World Cancer Congress
Biomedical significance and ameliorative potentials of inducible nitric oxide synthase (iNOS) inhibitors
in the development, progression and Metastasis of Prostate Cancer: A review
Lawrence Okonkwo Aka
St. Matthew’s University, British West Indies
Nitric oxide (NO) is synthesized in a variety of tissues and
organs in a reaction where the amino acid L-arginine
is converted into L-citruline. The enzyme catalyzing this
reaction is designated as nitric oxide synthase (NOS).
Inducible nitric oxide synthase (iNOS) is one of the three
different isoforms of nitric oxide synthase. Aside the desirable
effects of enhanced neurotransmission and vasodilation
produced by the constitutive isoforms (nNOS and eNOS),
the inducible isoform (iNOS) is associated with cytotoxicity
of macrophages and tumor-induced immunosuppression.
Expression of (iNOS) in various human tumors has been
classically demonstrated in which case it promotes the
progression of such tumors. The selective expression of iNOS
has been reported in human prostrate carcinoma and thus
nitric oxide consequently produced may have many roles in
the development, progression and metastasis of prostate
cancer. Prostatic intraepithelial neoplasia (PIN) significantly
characterizes the development and progression of prostatic
adenocarcinoma and has been associated with high levels
of iNOS. Interestingly debates over PIN distribution and
expression of (iNOS) is gaining momentum and points to
the potentials of inducible nitric oxide synthase inhibitors in
the amelioration of this development and progression. The
immunohistochemical examination of the activity of iNOS
in prostatic carcinoma has been significantly demonstrated
in both basal epithelial cells and secretory cells of the
glandular epithelium. Though nitric oxide produced by iNOS
can have cytotoxic and cytostatic effects on tumor cells, and
may act as tumor growth suppressors, its identified role
in promoting angiogenesis in tumor suggests that it may
stimulate tumor growth rather than inhibit it. There are
conflicting information on the specific role of NO in cancer
growth. While some hold the opinion of NO acting as a
tumor suppressor others suggest that it actually promotes
cancer growth hence a dual role. Recent findings suggest
that NO may be relevant for tumor progression through
at least two mechanisms: the stimulation of angiogenesis
and increased mutagenesis through the direct action of
free radicals on the DNA. In addition, NO released from
tumor cells is suggested to participate in the tumor-induced
immunosuppression via the anti-proliferative effect of NO
on tumor-infiltrating lymphocytes. Many evidences abound
regarding the strong association between iNOS expression
and rapid prostate cancer cell proliferation rate, depicting
a good predictor of poor survival in univariate analysis, but
was inferior to established prognostic factors in multivariate
analysis. From the various experimental observations, all
three isoforms of NOS can be involved in promoting or
inhibiting the etiology of cancer including prostate cancer in
humans. NOS activity has been detected in tumor cells of
various histogenetic origins and has been associated with
tumor grade, proliferation rate, and expression of important
signaling components associated with cancer development
such as the estrogen receptor. Increased NO generation in
a cell may select mutant P53 cells and contribute to tumor
angiogenesis by upregulating vascular endothelial growth
factor (VEGF). Due to the importance of NO in various
pathological processes including prostatic carcinoma, NOSes
are regarded as an important pharmacological target and
a great deal of effort has been made to design specific
NOS inhibitors. However, the high degree of similarity
among NOS isoforms poses an obstacle when attempting
to find a specific inhibitor of a particular isoform. From the
upcoming experimental observations on the expression
of NOS IN prostate carcinoma, it becomes very apt to
suggest that inhibiting the production of NO synthesis
by iNOS inhibitors would provide great opportunities
and potentials for the management and amelioration of
prostatic carcinoma. Therefore, an understanding of the
molecular dynamics of NO in prostatic carcinoma would be
very valuable in the development of drugs that potentially
can be helpful in adult male prostate cancer patients.
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