Plant Flavonoids on Cancer Treatment

This assignment explores the role of plant flavonoids in cancer treatment and prevention. It discusses DNA damage, repair mechanisms, and the etiology of cancer. It also covers cervical cancer, its risk factors, and different forms of cancer treatment. The assignment focuses on rutin, its anti-cancer benefits, and its role in reducing neuropathic damage. It also discusses different types of flavonoids and their effects as anticancer compounds.

Running head: PLANT FLAVONOIDS ON CANCER TREATMENT
PLANT FLAVONOIDS ON CANCER TREATMENT
Name of the student:
Name of the university:
Author note:

1
PLANT FLAVONOIDS ON CANCER TREATMENT
DNA or deoxy-ribonucleic acid is a molecule that contains the various types of
instructions that an organism needs for the development and living and reproduction. These
instructions are mainly found to be present inside the cell and these are passed from parents to
that of the children. Each nucleotide is seen to contain a phosphate group, a nitrogen group and
the sugar group along with four types of nitrogen like adenine (A), thymine (T), guanine (G) and
cytosine (C) (Roos et al. 2016). The order of these bases mainly determines the instructions of
DNA and their genetic codes. Endogenous cellular processes result in five types of DNA damage
like the oxidation of bases, alkylation of bases, hydrolysis of bases, bulky adduct formation and
mismatch of bases because of errors in DNA replication. Exogenous agents may result in
different damages like UV-B light causing cross-linking between adjacent thymine and cytosine
creating pyrimidine dimmers, UV-A light causing free radicals causing indirect damage,
Ionizing radiation breaking DNA strands and even thermal disruption and industrial chemical
effects (O’connor 2015). The different repair mechanisms are the direct repair, excision repair,
mismatch base repair and recombination repair.
Fig: DNA damage
Source: (O’connor 2015)

2
PLANT FLAVONOIDS ON CANCER TREATMENT
A large number of chemicals as well as various types of physical agents like that of UV light as
well as γ-radiation have been found to be intricately associated with the etiology of disorder of
cancer. These agents result in generation of DNA and damage and this becomes the first step in
the procedure of carcinogenesis. It is true that the evolutionary procedures have given rise to
different types of DNA repair tools that repair this damaged DNA (Tubbs et al. 2017). However,
in certain times, the replication of the damaged DNA takes place even before repairing can occur
particularly when they are induced at a high frequency. It has been also found that damaged
replication may also lead to various gene mutations that in turn gave rise to different altered
proteins. Mutation in the oncogenes that are actually tumor-suppressor genes or the genes that
control the cell cycles, result in generation of the colonal cell population that associates with that
of the distinct advantage of the proliferation. The stages like initiation, promotion, and
progression can also get subjected to exposure to carcinogens and these lead to induction of the
human cancer.
Cervical cancer occurs in the lower part of the uterus that remain associated with the
vagina. Studies suggest that various strains of human papillomavirus which is a sexually
transmitted infection play an important function in causing cervical cancer. The various signs of
the early stage cervical cancer is vaginal bleeding after that of the intercourse after menopause or
between periods. Foul smelling watery bloody vaginal discharge and pelvic pain and pain during
intercourse are also symptoms (Haradhvala et al. 2016). The different risk factors for this type of
cancer includes many sexual partners, sexually transmitted infections, early sexual activity,
weakened system and even smoking.
Worldwide cancer statistics have shown that there are 17 million cases of cancer
worldwide reported in the year 2018. Deaths were seen to be around 9.6 million worldwide as

3
PLANT FLAVONOIDS ON CANCER TREATMENT
per data obtained in 2018. In United Kingdom, 3126 cases of cervical cancer had been noted
down in the year 2015. However, the percentage of cervical cancer in comparison to that of total
cancer cases is less than 1% in the year 2015 in UK. The age of the people being affected by
cervical cancer as found in the reported cases in the year 2013-2015 in UK is 25-29 years (Yards
et al. 2016). Deaths in United Kingdom due to cervical cancer are found to be 854 in 2016. 63%
of the people is seen to survive cervical cancer for about 10 or more years in 2010-2011 in
England as well as in Wales. Researchers have also found out that 99.8% of the cervical cancer
cases are preventable in United Kingdom in the year 2015.
Fig: survival rate of colon cancer in UK.
Source: (Ashworth et al., 2017)

4
PLANT FLAVONOIDS ON CANCER TREATMENT
Fig: deprivation quintile in cancer
Source: (Ashworth et al., 2017)
Diet is now considered to be playing an important role in prevention f cancer and its
control as well. Recent evidences are of the opinion that diet can modify the risks of many types
of cancer like gastric, colorectal, lung, prostrate and breast. It is believed that more or less every
individual have similar nutritional requirements with exceptions of small differences between
gender and life stages (Jeggo et al. 2016). Advancements in genetic sciences have revealed that
as every individual is genetically unique, not everyone responds in a similar manner to specific
nutrients. Nutrigenomics which is mainly a new science domain helps in exploring the role of
different vitamins, bioactive food compounds, minerals in different types of gene expression and
also try to find out the effects that an individual variation can have on the response of the body to

5
PLANT FLAVONOIDS ON CANCER TREATMENT
specific foods. In this way, the subject can help in finding out how diet management can help in
prevention and control of cancer in individuals.
Rutin is a bioflavonoid or plant pigment that is obtained from invasive plant species
called Carpobrotus edulis and contribute to antibacterial properties of the plants. Apples, most
citrus fruits, figs, buckwheat and black and green tea are containing this flaovonoid. It is a
powerful antioxidant and helps the body to produce vitamin C and collagen (Ashworth et al.,
2017). It has many medicinal and health benefits like it helps in blood circulation, prevention of
blood clots, lowering of cholesterol, reduction of arthritis pain and many others. It was first
discovered in nineteenth century in buckwheat that contains about 15% in young leaves and 2-
10% of the total dry weight .
Rutin also called vitamin P has been found to be associated with anti-cancer benefits
where they decreases the migration of the cancer cells and also arrest the cell cycles in the G0-
G1 phase of the cell cycle. They can inhibit proliferation of cancer cells by inducing apoptosis
mediated through cell cycle arrest and activation of caspase protein. This would be further
discussed in the assignment in details (Abegglen et al., 2015).
Treatment of the cervical cancer is found to be dependent of a number of factors
like stage of the cancer, other types of health problems and the preferences of the patients. One
of the most important forms of treatment is surgery. Early stage cervical cancer is mainly found
to be treated with surgery that helps in removing the uterus hysterectomy. This is believed to
cure early stage cervical cancer and also helps by prevention of recurrence. Two types of surgery
might take place. One of them is simple hysterectomy where only cervix and uterus along with
that of cancer are mainly removed. Another is radical hysterectomy where cervix, uterus and

6
PLANT FLAVONOIDS ON CANCER TREATMENT
some parts of lymph nodes and vagina are also removed with cancer (Irianoto et al. 2017).
Another form of treatment is the radiation therapy that mainly utilizes high powered energy
beams like that of X-ray protons and also kills cancer cells. It has been found that radiation
therapy is also used alone or also that with chemotherapy before surgery for shrinking a tumor or
after surgery which becomes beneficial in killing remaining cancer cells. It can be provided
externally by directing the radiation beam at the affected portions of the body like that of the
external beam radiation therapy. Another one is internally which can be done by placing a device
that remains filled with radioactive material inside the vagina. This is mainly done only for few
minutes like in brachytherapy. Another form of treatment is the chemotherapy. This procedure
mainly utilizes medications that are usually injected in the vein for the killing of the cancer cells
(Knijnenburg et al. 2018). It has been found that lower the amount of the doses of chemotherapy
are often combined with radiation therapy by the healthcare professionals. This is mainly
because chemotherapy helps in enhancing the effects of radiation. Higher doses of chemotherapy
are mainly utilized for controlling advanced cervical cancer which is found to be not curable by
professionals. Chemotherapy can be also performed through the mouth or injected into the
muscles or veins. They travel the drug stream and thereby reach different cancer cells throughout
the body called the systemic chemotherapy. It might be placed directly into the cerebrospinal
fluid, an organ or a body cavity where the drugs act on the cancer cells in those areas called the
regional chemotherapy. Another form of treatment is called the Targeted therapy which is a type
of treatment that utilizes drugs as well as other substances for identifying and attacking specific
cancer cells without causing harm to any types of normal cells. Monoclonal antibody therapy is
one of the types of this therapy where antibodies prepared from single type pf immune cells are
used from the laboratories (George et al. 2017). They can identify important substances on the

7
PLANT FLAVONOIDS ON CANCER TREATMENT
cancer cells as well as normal substances that enhance the cancer cells for growth. The
antibodies are seen to get attached to the substances and thereby kill the different cancer cells
blocking their growth and keeping them from spreading. Another type of therapy is called the
immunotherapy. This mainly utilizes the immune system of the body for fighting cancer.
Substances that are mainly prepared by the body or in the laboratory can help in boosting,
directing and restoring the natural defense against cancer.
In the present generation, plants are providing an endless supply of different types of
secondary metabolites or that of phytochemicals that are exploited by the health industry to fight
various forms of cancer. It has been found that the efficacy of the compounds like flavonoids in
acting on the target molecules mainly depends on the absorption and their subsequent
metabolism, followed by distribution and then that of the availability at the site of action in the
body. Flavonoids are seen to be transformed into the structures of conjugate metabolites like that
of O-glucuronides, sulfate esters and O-methyl esters by phase II and hydrolyzing enzymes in
the small intestine, liver and colon (Russo et al. 2019). It has been found that Quercetin
glycosides can be better absorbed than another of its counterpart called the aglycone. They also
show higher plasma concentrations after they get transformed firstly in either deglycosylation
processes at the intestinal level or carrier-mediated transport. Studies are of the opinion that such
low doses of flavonoids usually does not interfere with the cell cycle procedure in case of normal
cells. However, it has been found that there are certain compounds like that of the 3-
hydroxyflavone, luteolin and apigenin show considerable toxicity when utilized in high doses
resulting in the increased ROS generation. They are also seen to disturb the cellular integrities by
enforcing several types of cell-death mechanisms in the normal cells (Abotaleb et al. 2019).
Now, researchers have understood that many external signals that include stimulation of growth

8
PLANT FLAVONOIDS ON CANCER TREATMENT
like that of the growth factors and those which inhibit growth like that of the DNA damaging
agents have the ability in controlling cell proliferations through the arresting of different cell
cycle at various phases of the cell growth. Therefore, researchers are now focusing on the
modulating effects of these flavonoids on the different cellular signaling pathways that are
involved in the DNA damage and repair. This has been found to become a novel approach in
chemoprevention. They are suspected to inhibit several points in that of the cancer progression
that includes invasion, metastatis, angiogenesis, and apoptotic mechanisms and different cell
cycle arrest. The various types of flaovonoids as well as their effects as anticancer compounds
are discussed below.
Rutin also called quercitin rutinoside is an antioxidant which has a very low reactivity
rate and they are seen to possess the strong desire of donating their spare electrons in supporting
and protecting the body. As a result of this generous ability in sharing, rutin is not only called an
anti-oxidant but also has many anti-cancer properties and anti-inflammatory properties that have
many health effects. It has been already found that most cancer treatments like radiation and
chemotherapy causes damage to the nervous system and also have many side effects like that of
peripheral neuropathy, chronic pain and headaches. There is also very little researches regarding
conventional cancer treatments that include anti-oxidants and oxidative stress. It has been found
that rutin can help in reduction of the neuropathic damage as well as the unwanted side effects
that come with it (Busch et al. 2015). This flavonoid is responsible for synergizing and
protecting the neurons in the dorsal horn of the spinal cord that play an important role in sensory
information and that of pain perception. Rutin treatment is seen to act as possible therapeutic
agents in treatment of leukemia, lung cancer, and breast cancer, colob cancer, endometrial and
ovarian cancer.

9
PLANT FLAVONOIDS ON CANCER TREATMENT
Fig: rutin
Source: (Iriti et al. 2017)
This is mainly use in chemotherapy and is included in a group of drug called the
alkylating agents. They mainly work by attaching to the DNA strands of one cancer cells. DNA
is called the genetic material of the cells which actually control the different functions of the
cancer cells. When this drug is seen to get attached with the cells and its DNA, the compound
makes the cancer cells unable to divide into new cells. When cells cannot divide, they eventually
die. In case of normal cells, cells are seen to divide and when cells touch each other, they stop
dividing because of contact inhibition. Cancer cells lose such ability and therefore, they carry on
their division cycles (Iriti et al. 2017). This drug attaches with their DNA and stops divining
resulting in destruction of the cells. The main issue that this drug is that it cannot identify
between normal and cancer cells and tend to kill all cells resulting in side effects. One of the
studies have suggested that them to be synthetic alkylating agents which are related chemically
to the nitrogen mustards with different types of anti-neoplastic and immunosuppressive
activities. It is seen that the drug gets converted to active metabolites called aldophosphamide

10
PLANT FLAVONOIDS ON CANCER TREATMENT
and phosphoramide mustard in liver and thereby they bind to DNA and inhibit DNA replication
and initiates cell death (Duan et al. 2016).
Hydroxyurea is mainly referred to be helpful as the chemotherapy treatment and is
mainly known by the brand name called Hydrea. This is extensively used for the treatment of the
chronic leukemia as well as in cervical cancer. For cervical cancer, they are mainly used in
combination with that of the radiotherapy and might be also used in the treatment of acute
myeloid leukemia, ovarian cancer and also in head and neck cancers. This form of chemotherapy
drug is mainly called anti-metabolites (Nasiri et al. 2016). Cancer cells need to continue making
and repairing DNA so that they can grow and multiply accordingly. This form of drugs can help
by stopping cells in making and repairing cells thereby preventing growth and spread of cancer
cells. These drugs often termed as anti-metabolites are cell-cycle specific where they are seen to
attack those cells at very specific phases in the cycle. Antimetabolites are mainly classifies
according to the specific types of the substance with which they interfere. Hydroxyurea is mainly
seen to be the ribo-nucleotide reductase inhibitor (Singh et al. 2016).
Cisplatin is found to play an important example about how small changes in the
molecular structure can result in huge differences in the biological activities. Cisplatin can be
considered as the tiny molecular structure that is composed of platinum ions being surrounded by
four ligands that are arranged in a square. It mainly comprises of two chlorides next two each
other along with amine ligands helping in treating cancer. When two chlorides are opposite to
each other, they cannot show any activity (Montagna et al. 2017). Inside the cell, Cisplatin is
seen to lose two of its chloride ions that help in creating a reactive species that are seen to form
bonds with the DNa bases. It has been found that because of this cis-geomtery of the bonds,
Cisplatin forms of crosslink between bases of the DNA with the most of them being formed at

11
PLANT FLAVONOIDS ON CANCER TREATMENT
the regions where guanine and adenine are close to each other in the same strand. It can also
form bonds between two strands. These crosslink cause severe problems when the cell tries to
read or replicate the DNA thereby causing death. In this way, cancer cells are killed (Zhikhoreva
et al. 2018).
Fig: DNA damage
Source: (Ashworth et al., 2017)

12
PLANT FLAVONOIDS ON CANCER TREATMENT
References:
Abegglen, L.M., Caulin, A.F., Chan, A., Lee, K., Robinson, R., Campbell, M.S., Kiso, W.K.,
Schmitt, D.L., Waddell, P.J., Bhaskara, S. and Jensen, S.T., 2015. Potential mechanisms for
cancer resistance in elephants and comparative cellular response to DNA damage in
humans. Jama, 314(17), pp.1850-1860.
Abotaleb, M., Samuel, S., Varghese, E., Varghese, S., Kubatka, P., Liskova, A. and Büsselberg,
D., 2019. Flavonoids in Cancer and Apoptosis. Cancers, 11(1), p.28.

13
PLANT FLAVONOIDS ON CANCER TREATMENT
Ashworth, A., Jackson, S., Martin, N. and Smith, G.C.M., INSTITUTE OF CANCER
RESEARCH ROYAL CANCER HOSPITAL and Kudos Pharmaceuticals Ltd, 2017. Dna
damage repair inhibitors for treatment of cancer. U.S. Patent Application 15/593,865.
Busch, C., Burkard, M., Leischner, C., Lauer, U.M., Frank, J. and Venturelli, S., 2015.
Epigenetic activities of flavonoids in the prevention and treatment of cancer. Clinical
epigenetics, 7(1), p.64.
Duan, X., He, C., Kron, S.J. and Lin, W., 2016. Nanoparticle formulations of cisplatin for cancer
therapy. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology, 8(5), pp.776-
791.
George, V.C., Dellaire, G. and Rupasinghe, H.V., 2017. Plant flavonoids in cancer
chemoprevention: role in genome stability. The Journal of nutritional biochemistry, 45, pp.1-14.
Haradhvala, N.J., Polak, P., Stojanov, P., Covington, K.R., Shinbrot, E., Hess, J.M., Rheinbay,
E., Kim, J., Maruvka, Y.E., Braunstein, L.Z. and Kamburov, A., 2016. Mutational strand
asymmetries in cancer genomes reveal mechanisms of DNA damage and repair. Cell, 164(3),
pp.538-549.
Irianto, J., Xia, Y., Pfeifer, C.R., Athirasala, A., Ji, J., Alvey, C., Tewari, M., Bennett, R.R.,
Harding, S.M., Liu, A.J. and Greenberg, R.A., 2017. DNA damage follows repair factor
depletion and portends genome variation in cancer cells after pore migration. Current
Biology, 27(2), pp.210-223.

14
PLANT FLAVONOIDS ON CANCER TREATMENT
Iriti, M., Kubina, R., Cochis, A., Sorrentino, R., Varoni, E.M., Kabała‐Dzik, A., Azzimonti, B.,
Dziedzic, A., Rimondini, L. and Wojtyczka, R.D., 2017. Rutin, a quercetin glycoside, restores
chemosensitivity in human breast cancer cells. Phytotherapy research, 31(10), pp.1529-1538.
Jeggo, P.A., Pearl, L.H. and Carr, A.M., 2016. DNA repair, genome stability and cancer: a
historical perspective. Nature Reviews Cancer, 16(1), p.35.
Knijnenburg, T.A., Wang, L., Zimmermann, M.T., Chambwe, N., Gao, G.F., Cherniack, A.D.,
Fan, H., Shen, H., Way, G.P., Greene, C.S. and Liu, Y., 2018. Genomic and molecular landscape
of DNA damage repair deficiency across The Cancer Genome Atlas. Cell reports, 23(1), pp.239-
254.
Montagna, E., Palazzo, A., Maisonneuve, P., Cancello, G., Iorfida, M., Sciandivasci, A.,
Esposito, A., Cardillo, A., Mazza, M., Munzone, E. and Lai, A., 2017. Safety and efficacy study
of metronomic vinorelbine, cyclophosphamide plus capecitabine in metastatic breast cancer: a
phase II trial. Cancer letters, 400, pp.276-281.
Nasiri, F., Kismali, G., Alpay, M., Kosova, F., Cakir, D.U. and Sel, T., 2016. Rutin enhances the
antiproliferative effect of 5-FU and oxaliplatin in colon cancer cells.
O’Connor, M.J., 2015. Targeting the DNA damage response in cancer. Molecular cell, 60(4),
pp.547-560.
Roos, W.P., Thomas, A.D. and Kaina, B., 2016. DNA damage and the balance between survival
and death in cancer biology. Nature Reviews Cancer, 16(1), p.20.

15
PLANT FLAVONOIDS ON CANCER TREATMENT
Russo, G.L. and Ungaro, P., 2019. Epigenetic Mechanisms of Quercetin and Other Flavonoids in
Cancer Therapy and Prevention. In Epigenetics of Cancer Prevention (pp. 187-202). Academic
Press.
Singh, A. and Xu, Y.J., 2016. The cell killing mechanisms of hydroxyurea. Genes, 7(11), p.99.
Tubbs, A. and Nussenzweig, A., 2017. Endogenous DNA damage as a source of genomic
instability in cancer. Cell, 168(4), pp.644-656.
Yard, B.D., Adams, D.J., Chie, E.K., Tamayo, P., Battaglia, J.S., Gopal, P., Rogacki, K.,
Pearson, B.E., Phillips, J., Raymond, D.P. and Pennell, N.A., 2016. A genetic basis for the
variation in the vulnerability of cancer to DNA damage. Nature communications, 7, p.11428.
Zhikhoreva, A.A., Belashov, A.V., Bespalov, V.G., Romanov, V.A., Semenov, A.L.,
Zhilinskaya, N.T., Semenova, I.V. and Vasyutinskii, O.S., 2018, June. Detection of
morphological changes in cisplatin-treated ovarian cancer cells by digital holographic
microscopy. In 2018 International Conference Laser Optics (ICLO) (pp. 577-577). IEEE.