Who Plays Dual Role in Cancerous and Normal Cells? Natural Antioxidants or Free Radicals or the Cell Environment
Received: September 18, 2012;
Accepted: November 26, 2012;
Published: January 04, 2013
In the recent years, the anticancer studies on the natural products and herbal
medicines have been increased with the idea that these compounds can kill cancer
cells or prevent their replication and progress. Most of the positive anticancer
effects of the natural products have been claimed related to their antioxidant
components. In the recent years most of studies support positive effects of
natural antioxidants in many debilitating human diseases such as diabetes (Hosseini
and Abdollahi, 2012), hyperprolactinemia (Hasani-Ranjbar
et al., 2010), infertility (Momtaz and Abdollahi,
2010), or aging (Hasani-Ranjbar et al., 2012;
Momtaz and Abdollahi, 2012) etc.
Medicinal plants produce diverse secondary metabolites, of which the most important
classes are phenolic compounds characterizing by at least one aromatic ring
(C6) and one or more hydroxyl groups. Antioxidant activity of phenolic compounds
is due to their high tendency to chelate metals by possessing hydroxyl and carboxyl
groups. The flavonoids and polyphenols can directly scavenge Reactive Oxygen
Species (ROS) such as superoxide, hydrogen peroxide, hydroxyl radical, or other
free radicals mainly by their ability to donate electrons or hydrogen atoms.
Therefore, reduced forms of phenolic compounds or some vitamins such as A, C
and E act as antioxidant, but phenoxyl radicals (the oxidized form) can cause
cytotoxicity especially via prolonging the lifetime of the radicals by spin-stabilization.
The phenoxyl radicals are generally toxic to living systems, by initiating free-radical
chain reactions in the membrane (Michalak, 2006). Thus,
it can be imagined that antioxidants play dual role in treatment and prevention
of cancer (Abdollahi and Shetab-Boushehri, 2012). This
may be due to the dual role of ROS in cancer, because the high levels of which
are either essential for cancer development or making them susceptible to ROS-induced
cell death in comparison to normal cells (Lopez-Lazaro,
Interestingly, a mode of action for some anticancer drugs involves the generation
of free radicals to cause cellular damage and necrosis of malignant cells. A
concern has gradually developed as How can antioxidant compounds reduce
the beneficial effect of chemotherapy on malignant cells? As for instance,
antioxidants are able to interfere with the oxidative mechanisms of alkylating
agents, which cause DNA damage and cell necrosis. It is notable that chemotherapy
damages are usually created by sort of other mechanisms toward apoptosis. Hence,
the argument that antioxidants are likely to interfere with most chemotherapies
cannot be extrapolated to all drugs. Although, there are no sufficient in
vivo evidences to confirm that vitamins E, C and A might reduce the efficacy
of chemotherapy but there are reports that beta-carotenes reduce the in vivo
effect of 5-fluorouracil on one type of tumor, and also vitamin C induces kind
of resistance to doxorubicin in resistant breast cancer cells (Lamson
and Brignall, 1999).
Furthermore, while many papers highlight the beneficial role of natural antioxidant
in cancer prevention, several clinical trials in the 1990s in different populations
brought up with different achievements such as reduction of gastric cancer cells
while increasing the lung cancer cells. As a result, the other question is How
might antioxidants prevent cancer? In fact, antioxidants wipe up free
radicals, by neutralizing the electrical charges and preventing the free radicals
taking electrons from other molecules. But the concern raised from this conception
is by which mode of action, a natural antioxidant is able to defense normal
cells against cancer inducers (http://www.cancer.gov/cancertopics/factsheet/prevention/antioxidants;
Omenn et al., 1994).
This concept is being more complicated when one discusses about the phenolic
compounds which are able to act as both antioxidant and pro-oxidant. The antioxidant
activity might enhance the growth occurring in transformed cells, but undesirable
pro-oxidant activity could damage the DNA and cellular membranes. However, cells
response because of abnormal regulatory function and activity depending on extracellular
and intracellular micro-oxygen environment can be different. Another challenge
facing the concept is the lack of sufficient computational biology approaches
to help researchers in this field.
Taking collectively, the main question still stands and so we recommend researchers
to try doing tests in both normal and cancerous cells simultaneously to predict
whether a natural antioxidant may show a beneficial or detrimental effect. To
reach convincing conclusions, it is important to mention that anticancer effects
of antioxidants mainly come from in vitro evidences while there are many
challenges on reliability of such models due to use of frequently passaged cultured
cells (Shetab-Boushehri and Abdollahi, 2012). Also,
it is essential to consider and identify the anticancer mechanisms more than
antioxidant effects for any compound that is hypothesized to be both antioxidant
and anticancer. Therefore, the question of whether an antioxidant compound can
be cytotoxic for cancer cells is still unanswered by current evidences.
Abdollahi, M. and S.V. Shetab-Boushehri, 2012.
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