Experimental Approach to Treatment of Colorectal Cancer by Herbs and Their Constituents: An Overview on in vivo and in vitro Protocols and Molecular Targets
Abdurrahman Al Diab,
Mohammad Farhan Qureshi,
Viquar Fatima Qureshi
Mohammad Rehan Qureshi
Behind the alluring fame of established drugs in a magical cure of some types of cancers are myriad toxicities. Hence, it became imperative to search alternative approaches of treatment. Although a large number of papers are published to show that herbs, plant products and their constituents are capable to inhibit the growth of a variety of human colon carcinoma cell lines, there is a gross neglect on an impact of in vivo outcome which show overall effects. The present study on an experimental approach to treatment of Colorectal Cancer (CRC) by herbs, plant products and their constituents was undertaken to review the (1) adverse effects of established drugs used against CRC, (2) herbs, plant products and their constituents as alternatives to established drugs, (3) in vivo studies on herbs, plant products and their ingredients, (4) in vitro studies on herbs, plant products and their ingredients, (5) pros and cons of in vivo and in vitro studies, (6) molecular targets and (7) conclusion. The articles included were peer reviewed English language articles published up to November 2011. These were selected from Pub Med, Pub Med Central, Science Direct, Up-to-date, Med Line, Comprehensive databases, Cochrane library and the internet (Google, Yahoo). The search strategy corresponded with points, 1-6 above. The literature obtained is reviewed. It is suggested that the laboratories working on CRC with in vitro protocol may also undertake confirmatory in vivo experimentation with an application of gene expression profiling using microarray technologies.
to cite this article:
Abdurrahman Al Diab, S. Qureshi, Mohammad Farhan Qureshi, Viquar Fatima Qureshi and Mohammad Rehan Qureshi, 2012. Experimental Approach to Treatment of Colorectal Cancer by Herbs and Their Constituents: An Overview on in vivo and in vitro Protocols and Molecular Targets. International Journal of Cancer Research, 8: 37-48.
December 29, 2011; Accepted: January 30, 2012;
Published: March 21, 2012
Notwithstanding the global efforts to find a definite and cost effective cure
for CRC, it remains the third most common malignancy and the third leading cause
of cancer death worldwide. The world records of CRC (both sexes) in 2008 showed
1234,000 cases diagnosed and 608,000 deaths (Globocan, 2008).
The ghastly reality entails miserable saga of the fatal ailment, which attract
world-wide efforts to find a cure. Reports in the literature (Al-Anazi
et al., 2011) do not associate gene polymorphism with colon cancer
susceptibility in Saudi Arabia, however; there are a number of risk factors
including diet poor in fibers and high in meat and fats (McKeown-Eyssen,
1994; Panala et al., 2009) in addition to
physical inactivity and obesity (Gunter and Leitzmann, 2006).
There are wide options of chemotherapy for treatment of CRC by established drugs,
however; they are well known for their adverse effects, including hepatotoxicity,
nephrotoxicity, neurotoxicity, in addition to metastasis and relapse (Taixiang
et al., 2005). Hence, in pursuit of finding alternatives to the established
drugs, there is an ongoing global search. The most suitable option remains the
herbs, plant products and their ingredients. Although, a large number of papers
are published to show that herbs, plant products and their constituents are
capable to inhibit the growth of a variety of human colon carcinoma cell lines,
there is a gross neglect on an impact of in vivo outcome which show overall
effects. Furthermore, very few experiments performed on herbs and plant products
and their ingredients involve gene expression profiling using microarray technologies.
This review is an attempt to gather information on the adverse effects of synthetic
drugs and the use of herbs, plant products and their constituents against treatment
of CRC by both in vivo and in vitro treatment protocols, the relevance
of in vivo experiments and application of gene expression profiling using
microarray technologies. The literature obtained is discussed and concluded.
Published articles selected for inclusion in this review are based on the significance
and understanding of literature search on adverse effects of synthetic drugs
used in the treatment of CRC and use of herbs, plant products and their constituents
in experimentation (in vitro and in vivo) against CRC, pros and
cons of in vitro and in vivo protocols, application of gene expression
profiling using microarray technologies. To meet this criterion, peer reviewed
English language articles published up to November 2011 were selected from Pub
Med, Pub Med Central, Science Direct, Up-to-date, Med Line, Comprehensive databases,
Cochrane library and the internet (Google, Yahoo). The search strategy combined
terms that included the title and the keywords, besides, the core of description
in the review.
REVIEW OF LITERATURE
The present study is a systematic collection of literature on (1) adverse effects of established drugs used against CRC, (2) alternative approaches to established drugs, (3) in vivo studies (herbs and plant products, formulation and mixtures, ingredients), (4)in vitro studies (herbs and plant products, formulation and mixtures, ingredients), (5) pros and cons of in vivo and in vitro studies, (6) molecular targets and (7) Conclusion.
Adverse effects of established drugs: Although, the established drugs
are known for their magical cure and fast relief, associated with them are innumerable
toxicities, besides, resistance, metastases and relapse. Ben
et al. (2011) reported that drugs that inhibit angiogenesis by targeting
Vascular Endothelial Growth Factor (VEGF) are often used in advanced cancers
including CRC. Although they are well tolerated, but cardiovascular and renal
side effects may appear. Furthermore, targeting the VEGF signaling pathway are
found to affect the normal function of endothelial cells in maintaining homeostasis
and can cause unwanted adverse effects. The emerging experimental evidence also
confirm that VEGF-targeting therapy caused less tumor cell-specific cytotoxicity,
allowing residual cells to become more resistant and develop a more malignant
phenotype (Chen et al., 2011).
A patient with advanced ascending colon cancer was admitted for surgery after
undergoing therapy with 15 courses of FOLFOX6 (first line), 6 courses of FOLFOX6+bevacizumab
(BV) (second line) and 3 courses of FOLFIRI+BV (third line). Upon admission
for surgery, she was diagnosed to have lung injury (with predominance of lymphocytes
without any evidence of infection). This was expected to be caused by anticancer
drugs, as treatment with steroids reversed the lung condition. The authors concluded
the lung injury to be due to irinotecan. Although, chemotherapy (S-1) was continued,
it proved ineffective and the patient died 27 months after operation (Komaki
et al., 2011). Oostendorp et al. (2010),
in a study on second-line irinotecan monotherapy for advanced CRC, found it
to be beneficial to the patients, but the treatment was associated with diarrhea,
nausea, vomiting and asthenia. The chemotherapy with irinotecan and oxaliplatin
before resection has been associated with steatohepatitis and vascular parenchymal
injury, respectively (Ryan et al., 2010).
Several anticancer drugs are known to cause cardiotoxicity as a major complication
however, incidence of Tako-Tsubo cardiomyopathy associated with anticancer drugs
is rare. Basselin et al. (2011) described a patient
on chemotherapy regimen with 5-fluorouracil, oxaliplatin, oxaliplatin and calcium
folinate (FOLFOX protocol) for colic adenocarcinoma to develop acute coronary
syndrome, which was similar to Tako-Tsubo syndrome. The patient developed cardiovascular
problems to the extent of cardiac arrest. Clinical limitations such as phlebitis
and catheter blockages are often observed with the administration of 5-fluorouracil
(5-FU) in combination with its synergistic biomodulator folinic acid in combination.
These combinations are known to have reduced efficacy and/or quality of life for
patients (Stutchbury et al., 2011). 5-Fluorouracil
(5-FU) used in treatment of various solid tumors, including colorectal, head and
neck cancers has been shown to cause hematological, digestive, cutaneous and neurotoxicity.
Neurotoxicity included drowsiness, acute confusion, seizure, confusion and signs
of metabolic encephalopathy, in addition to dysarthria and typical 5-FU-related
severe toxicities (e.g., neutropenia and mucosities) (Cordier
et al., 2011). Treatment with systemic fluorouracil is found to cause
sub-acute cutaneous lupus erythematosus (Almagro et al.,
Venous Thromboembolism (VTE), prevalent in most cancers including colon cancer
is known to have serious consequences, including high rate of recurrence, long
term anticoagulation and poor quality of life and death (Al-Diab,
2010). Colorectal patients treated with epidermal growth factor receptor
inhibitors develop dermatologic adverse drug reactions (Andreis
et al., 2010). Although, Oxaliplatin is known to cause hepatic sinusoidal
injury, it is one of the important drugs for the treatment of CRC. The hepatic
sinusoidal injury is evaluated by splenomegaly and thrombocytopenia. Many patients
of CRC, who were treated by FOLFOX therapy, had severe hepatic sinusoidal injury
(Toi et al., 2011). Burakgazi
et al. (2011) found oxaliplatin to cause irreversible sensory and
motor axon loss.
The 5-fluorouracil (5-FU) or Cisplatin treatment in murine colon carcinoma-induced
BALB/c mice were found to develop severe leucopenia, bone marrow suppression
and myelotoxicity (Son et al., 2011). In recent
years, the development of new and effective management options, such as fluoro-2-deoxy-D-glucose
(FDG) Positron Emission Tomography (PET), Total Mesorectal Excision (TME) and
monoclonal antibody novel "targeted" therapies have led to a considerable improvement
in the outcome of this disease however, these are yet to become common.
Alternative approach to established drugs: As less invasive option and
cost effective measures to disrupt the tumor cell cycle or inhibition of proliferation,
induction of apoptosis and improvement of the immune system, the use of herbs,
plant products and their ingredients do not lag behind in the therapeutic measures
of CRC (Wang and Yuan, 2008; Li
and Chi, 2011). The use of herbal medicine has tremendously increased during
the last 4 decades, because of the belief that they are non-toxic and possess
superior therapeutic effect as compared to established drugs.
An impressive body of data exists in support of the concept that food ingredients
(turmeric, cloves, ginger, aniseed, mustard, saffron, cardamom and garlic) can
be used in preventive strategies aimed at reducing the incidence and mortality
of different types of cancers, including CRC, because of their antioxidative,
antimutagenic and anticarcinogenic properties (Sengupta
et al., 2004). Literature reports suggest most of the herbs, which
are anti-inflammatory (Fukutake et al., 1998),
antioxidative, antimutagenic (Sengupta et al., 2004),
inhibit COX-1 and COX-2 activity (Fukutake et al.,
1998; Fukuda et al., 1999), cause ornithine
induce apoptotic activity, cytotoxicity (Kim et al.,
2006) and are immune restorative (Plotnikov et al.,
2005) are suspected to possess possible anticancer activity.
In vivo studies
Herbs and plant products: The herbs and plant products are often used as
a whole (powders, extracts, decoctions) in the treatment. Extracts of Coptidis
rhizoma and Scutellariae radix significantly inhibited AOM-induced
ACF formation (Fukutake et al., 1998). Coptidis
rhizoma and Scutellariae radix were found to suppress experimental colon
carcinogenesis and their preventive effects were attributed to their individual
ingredients berberine (Coptidis rhizoma) and baicalien (Scutellariae
radix) (Fukutake et al., 2000). Herbs Oren
(Coptidis rhizoma) and Ogon (Scutellariae radix) are found to
inhibit azoxymethane-induced aberrant crypt foci formation (Fukutake
et al., 2000). Asiamah et al. (2011)
reported Momordica charantia to inhibit the Azoxymethane (AOM) induced
Aberrant Crypt Foci (ACF) in Fisher 344 rats.
In a study on chemopreventive efficacy of garlic in an azoxymethane induced
rodent colon carcinogenesis model, Sengupta et al.
(2004) showed protective effects on colon carcinogenesis, as revealed by
significant inhibition of cell proliferation and induction of apoptosis, as
well as suppression of cyclooxygenase-2 activity, associated with significant
reduction in the incidence of aberrant crypt foci. Kaneshiro
et al. (2005) found that extracts of Hemerocallis fulva, Ipomoea
batatas, Curcuma longa and Nasturitum officinale caused marked
dose-dependent growth inhibition. Jianpi Huoxue herbs (JPHXH) are effective
in treating post-operational colonic cancer patients with Pi Deficiency Syndrome
to relieve the adverse reaction of chemotherapy (Liu et
Many herbs are known to possess potent immune-modulating effects. One such
is Ganoderma lucidum (Lingzhi), the polysaccharide functions of this
herb are reported to improve functions. A study to evaluate the effects of G.
lucidum polysaccharides on selected immune functions in patients with advanced
CRC showed that G. lucidum may have potential immuno-modulating effect
in patients with advanced CRC (Chen et al., 2006).
Herbal formulations and mixtures: To meet the desired therapeutic effects,
sometimes the herbs, plant products and their ingredients are used as formulations
or compound mixtures. Sanshishi (Gardeniae fructus) and the traditional herbal
medicine Oren-Gedoku-To (OGT), composed of Ogon, Oren, Sanshishi and Obaku,
have the chemopreventive potentials against colon cancer. The parameters were
aberrant crypt foci (Fukutake et al., 2000).
The authors further investigated the mechanism of action, by analyzing the influence
on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) activities and found
that both OGT and Sanshishi inhibited COX-2 but not COX-1, contributed to their
suppressive effects on ACF development. The results suggest that OGT may be
useful for colon cancer chemoprevention in terms of efficacy and toxicity (Fukutake
et al., 2000).
Herbal ingredients: Herbs and plant products contain hundreds of phytoconstituents
and/or ingredients, which are used against human diseases, including some types
of cancers. However, here we include the literature on ingredients which are
used against the treatment of CRC. Berberine and baicalin, major ingredients
of Coptidis rhizoma and Scutellariae radix, inhibited ACF formation
at a dose equivalent to the amount in each herbal extract (Fukutake
et al., 1998). The authors also found berberine and baicalein to
inhibit cyclooxygenase 2 and cyclooxygenase 1 activities, respectively.
Salicylic acid, a compound present in plants functions as a hormonal mediator
of the resistance response to the effect of pathogen and environmental stress.
Acetylsalicylic acid (aspirin; 2-acetoxybenzoic acid) is generally used for
pain relief and against inflammatory conditions and fevers. Literature reports
suggest that the regular use of aspirin is associated with decreased incidence
of certain cancers, particularly colon cancer (Paterson
et al., 2006). The exact mode of action is not known, however, the
authors propose that the anti-cancer effects of aspirin might be due to reduction
of the transcription of prostaglandin H (2)-synthase by salicylic acid which
might affect the synthesis of pro-inflammatory and potentially-neoplastic prostaglandins.
Salicylic acid is present in abundant range of herbs, spices, vegetables and
fruits of dietary relevance for lowering the risk of colon cancer.
Pentacyclic triterpenoid compounds, Ursolic Acid (UA) and Oleanolic Acid (OA)
are found in plants in the form of aglycones or as the free acid. These compounds
are used for their hepatoprotective, anti-inflammatory, antimicrobial, hypoglycemic,
antimutagenic, antioxidant and antifertility activities. In a study on the formation
of 1, 2-dimethyl-hydrazine (DMH)-induced Aberrant Crypt Foci (ACF) in the colon
of the male Wistar rat, Furtado et al. (2008)
found UA and OA to suppress the formation of ACF and have a protective effect
against colon carcinogenesis. The major active constituents of ginseng herbs
(American Ginseng and Notoginseng) are ginsenosides, which have been reported
to be effective in treatment of CRC (Wang and Yuan, 2008).
Mullauer et al. (2011) reported the development
and application of a liposome formulation of betulinic acid in mice. Liposomes
were incorporated with BetA and intravenously injected into Nude mice xenografted
with human colon and lung cancer tumors were effectively treated. The tumor
growth was greatly reduced, almost 50% and survival was good. The oral administration
of the liposomal formulation of BetA also slowed inhibition of tumor growth
without any signs of systemic toxicity. Any signs of systemic toxicity caused
by BetA treatment were absent. Liposomes are shown to be efficient formulation
vehicle for BetA, enabling its preclinical development as a nontoxic compound
for the treatment of cancers.
In vitro studies
Herbs and plant products: Kaneshiro et al. (2005)
reported crude extracts obtained from 44 herbal plants in the Ryukyu Islands,
might contain components capable of inhibiting the growth of a variety of human
colon carcinoma cell lines. Dichloromethane-methanol extract of Borassus
aethiopum Mart. is shown to induce apoptosis in human colon cancer (HT-29
cells) (Sakande et al., 2011). Jing
et al. (2011) found Boesenbergia rotunda to induce significant
inhibitions of colon cell line (HT-29). Solanum aculeastrum berries are
found to be anti proliferative against human colon cell line (HT-29) (Koduru
et al., 2006). Abd Malek et al. (2008)
showed weak cytotoxic activity of Pereskia bleo against human colon carcinoma
cell line (HCT 116). Aqueous extract of Fructus Ligustri Lucidi (AFLL) has been
shown to enhance the sensitivity of colon cancer cells (DLD-1) to doxorubicin-induced
apoptosis. The expression of Tbx3 was found to be repressed by AFLL upon the
activation of tumor suppressor genes (p14 and p53). These findings suggest that
AFLL has a chemotherapy potential in treatment of human colorectal carcinoma
(Zhang et al., 2011).
Herbal formulations and mixtures: PC-SPES, a mixture of eight herbs
has been shown to have antitumor activity against cancer cell lines of breast,
melanoma, and leukemia. The studies of the different components of this mixture
showed that these components, either independently or in combination are effective
against the tumor initiation and progression of colon cancer (Huerta
et al., 2002). In an evaluation of the anti-cancer activity of an
ethanol extract of Ka-Mi-Kae-Kyuk-Tang (KMKKT), a formula of ten Oriental herbs,
Lee et al. (2006) found that the extract suppressed
the invasion ability of the mouse colon 26-L5 cancer cells in vitro and
decreased their formation of liver metastasis when intraportally inoculated
in syngenic mice.
Tian-Xian liquid (TXL), a commercially available Chinese medicine decoction
has been used as an anticancer dietary agent for more than 10 years without
reported side effects. In a study on HT29 human colon cancer cell line and tumor-bearing
nude mice, Sze et al. (2011) demonstrate that
TXL possesses antiproliferative and antimetastatic activities and brings about
reversion of MDR on HT29 cell and on xenografted tissue in tumor-implanted nude
mice. The researchers also demonstrated the safety and quality of TXL extract.
Herbal ingredients: Monoterpenes, including geraniol found in essential
oils of herbs and fruits are suggested to be effective in cancer chemoprevention.
There was a 50% decrease of ornithine decarboxylase activity (a key enzyme of
polyamine biosynthesis, which is enhanced in cancer growth). There was a 40%
reduction of the intracellular pool of putrescine. Geraniol also activated the
intracellular catabolism of polyamines, indicated by enhanced polyamine acetylation.
These observations indicate that polyamine metabolism is presumably a target
in the antiproliferative properties of geraniol. There were no signs of cytotoxicity
or apoptosis detected (Chen et al., 2006).
The anticarcinogenic effects of eight flavanones (flavanone, 2-OH flavanone,
4-OH flavanone, 6-OH flavanone, 7-OH flavanone, naringenin, nargin and taxifolin)
were investigated in colorectal carcinoma cells (HT29, COLO205 and COLO320HSR).
Investigation on MTT assay showed 2-OH flavanone to have the most potent cytotoxic
effect on these three cells, both in vivo and in vitro (Shen
et al., 2004). In a study on parallel treatment of Huangqi compounds
and chemotherapy, Taixiang et al. (2005) found
that the compounds of herbs may stimulate immune-competent cells and decrease
side effects in patients treated with chemotherapy.
Betulinic acid (BetA) is a plant-derived pentacyclic triterpenoid which is
known to have effective in vitro activity against several cancers, including
colorectal, prostate, lung, cervix and breast cancer, melanomas, neuroblastomas
and leukemias. There are no cytotoxic effects of the compound against healthy
cells which projects BetA a promising candidate against cancer treatment. Nevertheless,
due to the solubility problems, it was difficult to study this compound in
vivo (Mullauer et al., 2011).
Polyphenols in herbs, fruits, soybean and vegetables are known to act as bioactive
components related with prevention of cancer by inducing apoptotic activity.
In a study on apoptotic effects of red wine polyphenols on human colon cancer
cells (SNU-C4), Kim et al. (2006) found increase
in the apoptotic activity, as revealed by different relevant parameters. The
Caspase-3 activity was significantly increased suggesting that polyphenols have
a strong potential for development as an anti-colon cancer agent. Beta-elemene,
a natural compound extracted from over 50 different Chinese medicinal herbs
and plants, has been effective in the treatment of brain, breast, cervical,
colon and lung carcinoma cells (Li et al., 2010).
Pros and cons of in vivo and in vitro studies: There are
a large number of papers published on herbal products and their ingredients
to show their capability to inhibit the growth of a variety of human colon carcinoma
cell lines (Kaneshiro et al., 2005). However,
the studies on in vivo effect are neglected. Literature reports suggest
similarity of in vivo protocol to clinical trials, in addition to its
superiority to in vitro investigations (Jeffrey, 2007).
The experiments involved in the discovery of new drugs cannot rely on in
vitro test methods, because these methods do not resemble the drug biotransformation
in vivo in liver. In past few decades, several in vitro human
liver models (supersomes, microsomes, cytosol, S9 fraction, cell lines, transgenic
cell lines, primary hepatocytes, liver slices and perfused liver) have been
developed, but each model has several or specific drawbacks, which prevent their
widespread use and acceptance by regulatory authorities as an alternative for
in vivo screening (Brandon et al., 2003).
In vivo is an experimentation that employs a whole living organism as
opposed to a partial or an in vitro in a controlled environment. Animal
testing and clinical trials remains the ultimate two forms of in vivo
research. In vivo testing is often preferred over in vitro protocol
because it is better suited for observing the overall effects of an experiment
on a living subject (Jeffrey, 2007) however, in vivo
experimentation is losing a common application. However, the experiments conducted
on in vivo studies have their own demerits. They involve cumbersome methods
to obtain the colorectal tissue and sacrifice of many animals at different stages
of progression. Nevertheless, during the early part of the third millennium,
visual colonoscopy was developed in mice with a traditional pediatric cytoscope
(2 mm diameter, rigid) to identify raised tumors by surface topology. With this
discovery, the method of serial sacrifice of animals can be substituted by the
method of Murine colonoscopy that can allow time to time evaluation and mucosal
biopsies of the same animal (Huang et al., 2002).
It is interesting to note that extensive investigations have been undertaken
on the transplantable tumors during the last 2 to 3 decades. The goal of these
studies was to improve techniques in cancer therapy that can combine both in
vitro and in vivo evaluation, simultaneously (Ozaslan
et al., 2011). While experimental tumors have great significance
for the purposes of modeling, Ehrlich Ascites Carcinoma (EAC) is one of the
commonest (Ozaslan et al., 2011). The peritoneal
cavity of the animal serves as the most sterilized natural incubator for the
growth of the malignant cells allowing almost all the studies, including chemotherapy,
survival time, body weight changes, total ascitic volume, cytotoxicity of the
EAC cells, impact of preventive agents on biochemical, molecular and genetic
changes and toxicity (Qureshi et al., 2000, 2001;
Asiri, 2009; El-Naggar et al.,
2011). Literature reports suggest positive indication of the anti-carcinogenic
potentials of a number of herbs, plant products and their ingredients including,
Commiphora molmol (Qureshi et al., 1993;
Al-Harbi et al., 1994), Macrosolen parasiticus
(Sodde et al., 2011), Ocimum sanctum (Islam
et al., 2011) and anethole (Al-Harbi et al.,
Although, the prognosis for patients with early stage colon cancer is good,
but majority of these cancers are diagnosed at later stages. Most drug development
strategies use transplantation of human tumor cells into genetically engineered
mouse models, which make them a suitable platform for biomarker discovery, study
of cancer biology and preclinical therapeutic trials (Hung
et al., 2010). There are many animal models for different cancers
in humans which can be used for in vivo experiments. Mice and rat models
for the study of colonic aberrant crypt foci induced by azoxymethane (Panala
et al., 2009) is one such example, which can analyze quite a lot
of preventive agents against CRC (Adhami et al.,
Molecular targets: Many techniques (X-ray, imaging, computed tomography
scan, magnetic resonance imaging, auto-fluorescence) have been employed in early
detection, diagnosis and prognosis of the malignant diseases (Masilamani
et al., 2004, 2011). However, the significance
of genetic changes has not been realized. The knowledge of genetic changes that
cause colorectal cancer has important ramifications for prevention, detection
and treatment of this disease (Fahy and Bold, 1998).
The techniques of gene array and proteomics have been used to investigate the
response of colo-rectal cancer cells to chemotherapeutic agents, including butyrate
(Williams et al., 2003). Mariadason
et al. (2004) reported use of gene expression profiling as a tool
to customize chemotherapy in colon cancer is an attainable goal in the foreseeable
future. The regulation of gene expression in a post-transcriptional manner can
be regulated by non-coding RNAs called MicroRNAs. These MicroRNAs play a major
role in regulation of cell proliferation, differentiation, apoptosis and immunity.
Their link with cancer progression, angiogenesis, metastasis and chemotherapy
resistance of tumors has become vital issues in epigenetics of cancer (Liu
and Chen, 2010). The application of MicroRNAs techniques as biomarkers in
diagnosis and prognosis and treatment of cancer will be a boon to researches
in development of novel therapeutic agents against CRC. Taken together, the
innovations in researches on CRC can be used in improvement in the prevention,
detection and treatment of the disease, however, these ramifications are yet
to reach the common laboratory.
The established drugs used in the treatment of CRC are well known for their adverse effects, hence; there has been always a pursuit for safe alternatives. In view of their most publicized non-toxic nature, the herbs and their ingredients are given priority. Currently, there is a wide range experimentation on their therapeutic potentials by in vitro protocol, while the in vivo method is grossly neglected, despite of the fact that the in vitro experiments do not resemble the drug biotransformation in vivo. Nevertheless, the experiments conducted on in vivo studies involve burdensome and time consuming methods to obtain the colonic tissue with sacrificing many animals at different stages of progression of the disease. Although, the more sophisticated methods of colonoscopy in rodents do exist, but they are yet to become common. Furthermore, the post-genomic technology has revolutionized our ability to characterize and recognize the molecular profiles to identify more effective and better tolerated preventive agents, however; very few experiments performed on herbs, plant products and their ingredients involve gene expression profiling using microarray technologies. It is suggested that the laboratories working on in vitro protocol may also undertake confirmatory in vivo experimentation with an application of gene expression profiling using microarray technologies.
Grant from Colorectal Cancer Research Chair, Department of Medicine, College of Medicine, King Saud University is acknowledged with thanks.
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