molecules
Review
Potential Treatment of Breast and Lung Cancer Using
Dicoma anomala, an African Medicinal Plant
Alexander Chota , Blassan P. George and Heidi Abrahamse *
Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011,
Doornfontein 2028, South Africa; chotatimzy@gmail.com (A.C.); blassang@uj.ac.za (B.P.G.)
* Correspondence: habrahamse@uj.ac.za; Tel.: +27-11-559-6550; Fax: +27-11-559-6448
Academic Editor: Silvie Rimpelová
Received: 21 August 2020; Accepted: 25 September 2020; Published: 27 September 2020
Abstract: Globally, cancer has been identified as one of the leading causes of death in public health.
Its etiology is based on consistent exposure to carcinogenic. Plant-derived anticancer compounds are
known to be less toxic to the normal cells and are classified into acetylenic compounds, phenolics,
terpenes, and phytosterols. Dicoma anomala is a perennial herb belonging to the family Asteraceae
and is widely distributed in Sub-Saharan Africa and used in the treatment of cancer, malaria, fever,
diabetes, ulcers, cold, and cough. This review aimed at highlighting the benefits of D. anomala in
various therapeutic applications with special reference to the treatment of cancers and the mechanisms
through which the plant-derived agents induce cell death.
Keywords: Dicoma; cancer; bioactive compounds; medicinal plants
1. Introduction
Cancer has been identified as a major public health problem globally. In the United states, cancer is
one of the leading causes of mortality [1]. In Sub-Saharan Africa, prostate, breast, and cervical cancers
are the most common with high incidence rates. The occurrence of these cancers in Sub-Saharan
Africa is estimated to double up in next 20 years [2]. The cancer incidence rate is estimated to increase
50% by 2030; the burden is mostly expected to increase in low- and middle-income countries [3].
The incidence and mortality rate of cancer in low- and middle-income countries are significantly
increasing, and Zambia is of no exception [4]. In South Africa, the incidence rate and treatment options
of lung cancer differ between provinces because the country is diverse in terms of culture and racial
groups [5]. Although the incidence rate of cancer in Africa is low when compared to other continents
in the world, the mortality rates are, however, higher, which significantly reflects poor therapeutic
outcomes [6].
The risk factors associated with cancers are divided into two categories based on their biological
nature and modifiability. These are intrinsic and non-intrinsic risk factors. Intrinsic risk factors are
simply random errors, which occur during DNA replication. Non-intrinsic risk factors are furthermore
divided into endogenous and exogenous risk factors. Endogenous factors include gender, biological
aging, genetic susceptibility, hormones, growth factors, and inflammation. While exogenous factors
include radiation, chemical carcinogens, tumor-causing viruses, bad lifestyles such as smoking,
alcohol consumption, nutrition imbalance, and lack of exercise [7]. There are different approaches
that are being used in the treatment and management of cancer such as chemotherapy, radiotherapy,
surgery, gene therapy, and immunotherapy [8,9]. Although these modern therapies have shown some
effectiveness in the treatment of cancer, they also have adverse side effects [8]. Therefore, the research
is focusing on plants and plant-derived agents to develop potent drugs to treat cancers. Many plant
species have shown medicinal properties that are used in the treatment and prevention of various
diseases [10]. However, it has been estimated that 50–60% of people living with cancer in the United
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States utilize plant-derived agents as an alternative therapy. These plants derived agents may be
administered alone or simultaneously with other therapies such as chemo or radiotherapy [11].
2. Dicoma Genus
The word Dicoma is derived from two Greek words “di” (two) and “Kome” (tuft hair) and the
word “anomala” is of Latin origin means irregular. D. anomala is widely distributed in African countries
such as South Africa, Angola, Burundi, Botswana, Democratic Republic of Congo (DRC), Rwanda,
Tanzania, Zambia, and Zimbabwe [12]. D. anomala is mostly grow in grassy and savanna areas [13].
The genus Dicoma has more than 10 species (Table 1).
Table 1. Shows the general taxonomy and common Dicoma species.
Kingdom
Plantae
Phylum
Magnoliophyta
Class
Magnoliopsida
Order
Asterale
Family
Asteraceae
Genus
Dicoma
Species
•
•
•
•
•
•
•
•
•
•
•
•
•
anomala
arenaria
capensis
fruticosa
galpinii
kurumanii
macrocephala
montana
picta
prostrata
schinzii
swazilandica
tomentosa
3. Dicoma anomala
Dicoma anomala (D. anomala) is commonly known as fever or stomach bush; it is a perennial
herb belongs to the family Asteraceae. It has an erect stem covered with thin hairs and bears a tuber
underground [14]. As shown in Figure 1, D. anomala leaves are narrow, stalkless, and positioned onto
the stem.
The leaves of D. anomala are rough and green, but most of the time, it appears grey. The flower
appears like a cup with terminal heads that look white-pinkish in color [12]. It is a native plant
in Sub-Saharan Africa. In South Africa, D. anomala is widely distributed across the country and is
predominantly found in Limpompo, Gauteng, North-West, Mpumalanga, KwaZulu-Natal, Free State,
and Northern Cape provinces [15]. In Africa, D. anomala plant has been used in the treatment of various
diseases such as fever, diabetes, ulcers, cold, and cough [14]. The ethnomedicinal use of D. anomala
are wide; its roots are extensively used in the therapy of at least 66 diseases that affect humans and
animals. However, South Africa has the highest number of ethnomedicinal uses of D. anomala with at
least 37 records for the treatment of various human illnesses [12]. Various medicinal uses of D. anomala
species are shown in Table 2.
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Figure 1. Dicoma anomala habitat. Dicoma anomala plant from eastern province of Zambia.
Table 2. The medicinal uses of D. anomala Sond.
Habitat
Stony grasslands,
rocky hillsides, and
savanna forests.
Altitude from 165 to
2075 meters.
Part(s) Used
Medicinal Use
Country Practiced
Roots
Abdominal Pain
Zimbabwe
Roots
Cardiovascular Diseases
Namibia and South
Africa
Tuber
Asthma
South Africa
Leaves and roots
Breast Cancer
Lesotho
Roots
Cataracts
Zimbabwe
Leaves and roots
Diabetes
Lesotho and South Africa
Root
Renal Problems
Swaziland and South
Africa
Root
Malaria
Zimbabwe
Root
Pneumonia
South Africa and
Zimbabwe
Root
Syphilis
Zimbabwe
Root
Cough
Malawi, Namibia, and
South Africa
Root
Hemorrhoids
Namibia
Root
Intestinal warms
Lesotho, Malawi, and
South Africa
Flower and roots
Wounds and sores
Lesotho, Malawi, and
South Africa
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4. Role of Plants in Cancer Therapies
Plants play a very important role in the treatment of cancer. This is because many plant species
possess novel chemicals that act as anticancer agents. The plant derived anticancer agents are shown
to exhibit less side effects compared to many chemotherapeutic agents [16]. In past years, herbs were
used as a major treatment for various cancers in different including countries in Europe and the
Middle East. According to various reports from the World Health Organization, many countries use
herbal medicine as an approved cancer treatment. It is estimated that only 5–15% of the herbs used
in the treatment of cancer have been investigated for their anticancer properties [17], and 50,000 to
80,000 plants worldwide are being used for various medicinal purposes [18].
In order to prevent and reduce cancer incidence, researchers are trying to find alternative
anticancer agents that will reduce the development of resistance caused during the chemotherapies [19].
Two-thirds of cancer therapies are derived from plant-based agents, and they are classified based on
their mechanism of action. A classic example of reactive oxygen species (ROS) inducer is thymoquinone,
a bioactive compound extracted from plants [17]. Apart from thymoquinone, Table 3 shows other
plant-derived phytochemicals used in cancer therapies.
Table 3. Shows phytochemical compounds and their role in cancer therapies.
Plant Name
Phytochemicals
Role in Cancer Therapy
Reference
Nigella sativa
Thymoquinone
Targets the signal transducer and activator of
transcription factor 3 (STAT3) pathway thereby
leading to the inhibition of cancer cell
proliferation.
[20]
Apigenin
Targets intrinsic apoptotic pathways. In lung
cancer, apigenin exert its effects by modulating
signals between Akt and Snail/Slung signaling
pathways leading to metastatic restrain of
cancer cells.
[21]
Zingiber officianale
6-Shogaol
Targets Akt and signal transducer and activator
of transcription (STAT) signaling pathways. In
NSCLC, 6-Shogaol directly regulates Akt1/2
pathways, which will in turn lead to the growth
inhibition or induce apoptotic cell death.
[22]
Thymus vulgaris
Thymol
Targets the mitochondria and its effects induce
mitochondrial malfunction and apoptosis of
cancer cells.
[23]
Scutellaria
baicalensis
Baicalein
Targets mitogen-activated protein kinase
(MARPK), extracellular signal-regulated kinase
(ERK), and p38 signaling pathways. In colon
cancer, Baicalin induces apoptosis and growth
suppression.
[24,25]
Glycyrrhiza glabra
Glycyrrhizin
Targets thromboxane A2 (TxA2) and signal
transducer and activator of transcription
(STAT) pathways.
[26]
Oldenlandia diffusa
Ursolic acid
Targets and interferes with cancer protein Ki-67,
CD31, and microRNA 29 (miR-29a).
[27]
Melilotus officinalis
Dicumarol
Targets pyruvate dehydrogenase kinase 1
(PDK1) leading to the interference of the
intrinsic apoptotic pathway
[28]
Licochalcone A
Targets cyclins and cyclin-dependent kinases
(CDKs). Their interaction with the cyclins and
CDKs results in cell cycle arrest in the G0 or G1
and G2 or Mitotic phases.
[29]
Petroselinum
crispum
Glycyrrhiza glabra
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5. Mechanisms of Plant-Derived Agents Induced Cell Death
The mechanism of action of plant-derived bioactive compounds involves inhibition of various
cellular activities, and the potency of plant-derived chemical agents is dependent on the dosage [30].
Figure 2 illustrates various steps involved in tumor development and its fate. The first step involves
the interaction of carcinogenic agents and reactive oxygen species (ROS) in the cell. Once inside,
the carcinogens will interact with the genetic material of the cell leading to mutations. On the other
hand, ROS interfere with the proteins and enzymatic activities of the cell. In step 6, the normal cell
transforms into a cancerous cell, and step 7 shows the proliferation of cancer cells. The continuous
proliferation of cancer cells leads to the formation of a tumor (step 8).
Figure 2. Carcinogenesis and the mechanism of action through which plant-derived bioactive
compounds induce cell death.
There are many studies conducted in the past decades. These studies reported that the in vitro
activities of medicinal plants have originated from Egypt and Asian countries [18]. However,
the mechanism of action of plant-derived bioactive compounds is dependent upon the quality and
quantity of the phytochemicals present in them. As illustrated in Figure 2 (steps 9 and 10), the bioactive
compounds are extracted from different parts of the plant and administered on the cancer cells. Once the
cancer cells are treated with bioactive compounds, the cancer cells will then have two fates, as shown
in steps 11 and 12, respectively. Under step 11, the cancer cells become normal after the treatment
with bioactive compounds or the cells may enter in the apoptotic cell death phase by the action of
phytochemicals (step 12) [16].
The possible mechanism of action of plant-derived phytochemicals are shown in Figure 3,
which involves either the activation or inhibition of cellular pathways. Bioactive compounds extracted
from natural sources promote apoptotic pathways, immune responses, and autophagy and inhibits
different phases of cell cycle as well as the migration and invasion of cancerous cells. It is scientifically
evident that scutellarein phytocompounds possess anticancer properties against a broad spectrum of
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cancers, including breast, colon, lung, prostate, renal, and tongue cancers. These phytocompounds
induce tumor cell death through multiple cellular pathways. The molecular targets include apoptosis,
cell cycle arrest, and proliferative inhibition pathways [31]. Scutellarein play an important role in tumor
suppression in prostate cancer cells. They induce tumor cell death through upregulation of caspase 3, 9,
G2/M-phase cell cycle arrests and Bax/Bcl-2 ratio, as shown in Figure 4 [16]. Scutellarein are also able to
induce apoptotic activities in liver cancer cell line HepG2 through activation of caspase-3 enzymes and
STAT3 signaling pathway [32]. This phytochemical is also able to suppress the invasion and migration
of human hepatocellular carcinomas via inhibition of Akt-STAT3/Girdin activities [33]. This anticancer
agent suppresses tumor growth and induces apoptotic activities against human colorectal cancer
by regulating p53 [34]. In breast cancer, scutellarein inhibits tumor proliferation and inversion via
upregulation of Hippo/Yap signaling pathways [35].
Cirsimaritin is a flavonoid with diversified pharmacological activities including antioxidant,
anti-inflammatory, antimicrobial, anticancer, and enzyme inhibitory activities. This bioactive compound
belongs to a class known as 7-O-methylated flavonoid [36]. Its anticancer activities have been
explored using different cancer cell lines, such as breast, lung, and gallbladder [37]. This anticancer
compound plays a vital role in angiogenesis inhibition through the downregulation of p-Akt, p-ERK,
and VEGF in MDA-MB-231 breast cancer cells [38]. In human gallbladder carcinoma GBC-SD cells,
cirsimaritin inhibits the growth of cancerous cells through mitochondrial apoptosis. Cirsimaritin
triggers endoplasmic reticulum stress by forming ROS, and it downregulates the phosphorylation of
Akt [39].
Figure 3. Possible mechanisms of action induced by plant-derived phytochemicals.
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Figure 4. General cell death signaling pathways induced by plant-derived bioactive compounds.
β-farnesene is one of the essential sesquiterpenes used in the treatment of different types of
cancer including breast, lung, and prostate [40–42]. This organic compound is suppressing tumor
proliferation through tumor apoptotic pathways. In tumor apoptotic pathway, ROS are formed and
induce mitochondrial damage leading to cytochrome c release. The released cytochrome c together
with Apaf 1 creates apoptosome that activates caspase cascade to induce cell death [43].
β-sitosterol is an important plant-derived bioactive compound used for the treatment of different
medical conditions. It has diversified medicinal benefits such as anti-inflammatory, antioxidant,
antidiabetic, antifertility, antimicrobial, immunomodulatory, and anticancer properties [44]. β-sitosterol
inhibits tumor cell proliferation and activates the apoptotic pathway of various cancer cell lines.
Cancer cell lines through which β-sitosterol exerts its anticancer activities include, breast, colon, lung,
gastric, and prostate cancers [45]. In A549 cells, β-sitosterol target the enzyme Trx/Trx1 reductase to
induce apoptosis through ROS and p53 activation [46]. β-sitosterol anticancer activities have been
explored and induce endoreduplication in HL60 and U937 cell lines via PI3K/Akt and Bcl-2 pathways.
In pancreatic cancer cell lines, β-sitosterol inhibits tumor cell growth, inducing G0/G1-phase cell cycle
arrest, and apoptotic activities, downregulates NF-kB activities, upregulates the expression of Bax,
and downregulates the expression of Bcl-2 protein [47].
A-Humulene is a naturally occurring bioactive compound isolated from Eupatorium odoratum L
and has been explored for its anticancer properties. This compound uses various pathways to induce
tumor cell death. In vitro effects of α-Humulene include increased production of ROS and inhibition
of Akt activation [42,48].
6. Major Anticancer Compounds of Dicoma
There are various compounds that are extracted from Dicoma species. Out of all the Dicoma species,
D. schinzii, D. capensis, D. anomala, and D. zeyheri have been investigated for medicinal use and were
classified based on their phytochemical composition. However, only one species (D. schinzii) out of
the four exhibited similarities in terms of bioactive compound composition. These compounds are
classified into different groups: acetylenic compounds, phenolic acids, flavonoids, sesquiterpenes,
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triterpenes, and phytosterols. These natural compounds derived from plants are seen to be non-toxic
to non-cancerous cells or normal cells, and these compounds are used in the treatment of different
cancers such as breast, ovarian, prostate, and kidney [12,49].
The roots and leaves of Dicoma anomala are extensively used in the treatment of various diseases in
Africa (Table 2). D. anomala extracts exhibit anticancer properties that are widely used in the treatment
of breast and lung cancers. The polyphenolic compounds from Dicoma species such as flavonoids,
sesquiterpenes, phytosterols, and triterpenes, as shown in Table 4, are considered to exhibit anticancer
properties [12].
Table 4. The structure of major plant-derived anticancer compounds.
Anticancer Agent
Structure
Classification
Reference
Sesquiterpenes
[50]
Sesquiterpenes
[51]
Cirsimaritin
Flavonoids
[52]
Scutellarein
Flavonoids
[53]
β β-sitosterol
Phytosterols
[54]
α
α
α
α
α-Humulene
β
β
β β-farnesene
β
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ββ
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Table 4. Cont.
Anticancer Agent
Structure
Classification
Reference
Stigmasterol
Phytosterols
[54]
Taraxasterol
Phytosterols
[55]
Lupeol
Triterpenes
[56]
Lupenone
Triterpenes
[57]
7. D. Anomala and Pharmacological Studies
Dicoma anomala is a perennial herb that is widely distributed in Sub-Saharan Africa. Its aerial
parts have been analyzed for the presence of phytochemical compounds [15]. D. anomala has been
studied for its pharmacological potential in the treatment of various diseases. D. anomala extracts are
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reported for their antibacterial, anti-inflammatory, antiviral, antioxidant, anticancer, and antiplasmodial
properties [58].
Vlietinck et al. (1995) evaluated the antibacterial properties of D. anomala root extract against various
microorganisms including Microsporum canis, Candida albicans, Staphylococcus aureus, and Trichophyton
mentagrophytes using agar well diffusion and dilution methods. Furthermore, they investigated the
effects of D. anomala root extract on viruses such as coxsackie, herpes simplex, measles, semliki forest,
and poliomyelitis through viral titer reduction [12].
Becker et al. [59] evaluated in vitro antiplasmodial activities of D. anomala subsp. Gerrardii extract.
Phytochemicals such as eudesmanolide and dehydrobrachylaenolide were isolated and used in
the in vitro parasite lactate dehydrogenase assay against plasmodium falciparum (p. falciparum).
Dehydrobrachylaenolide demonstrated anti-malarial activities against plasmodium falciparum.
Furthermore, D. anomala has anticancer properties that have motivated the researchers to focus
on the field of biomedicine. Shafiq et al. [53] evaluated the in vitro antiproliferative effects of silver
nanoparticles synthesized from the roots of D. anomala Sond. against MCF-7 breast cancer cells and
NF54 parasitic strains. The study revealed that silver nanoparticles conjugated sesquiterpene have
antiparasitic activities against NF54 p. falciparum strain, and it exhibited anticancer properties by
inducing oxidative damage in breast cancer cells. Asita and colleagues evaluated the modulation of D.
anomala and Cyclophosphamide (CP) in mutagen induced genotoxicity [60].
Steenkamp and Gouws in 2006 evaluated the cytotoxic properties of six plant extracts used in
cancer therapy in South Africa. In the study, aqueous extract from Dicoma capensis demonstrated
anticancer properties against three different breast cancer cell lines such as MCF-7, MDA-MB-231,
and MCF-12A. The aqueous root extracts from Dicoma anomala were investigated for the possible
postprandial extenuation in hyperglycaemia and how it modulates the activities of carbohydrate
metabolising enzymes [14]. Balogun and Ashafa evaluated the activities of D. anomala and Gazania
krebsiana used by Basotho for the treatment of various diseases [61].
8. Cancer Stem Cell Treatment
Stem cells are unspecialized body cells that have the ability to replicate and make well-differentiated
specialized cells. These cells are isolated from inner mass of a cell, which is 5–8 days old. The use
of stem cells in a clinical setup is restricted due to ethical, legal, and religious controversies [62].
Stem cells can be obtained from two main sources: adult and embryonic cells such as blood and
placenta [62,63]. Stem cell therapy has various applications in a clinical setup including, cardiac,
brain, skin, liver, and cancers [64]. The mechanism through which D. anomala regulates the cancer
stem cell activities is not clear, but various studies show effective regulation of cancer stem cell
signaling pathways. However, many plant-derived anticancer compounds target the surface targeting
antibodies of cancer stem cell (CSC), such as those found on breast cancer stem cells (anti-CD133, CD44,
and anti-EpCAM). These anticancer compounds may also target the ABC cassette, immune-evasion
antibodies, and cytokines [65].
9. Breast Cancer
According to the global burden of disease (GBD) report of 2015, cancer is the second leading
cause of death globally [66]. The global statistics show that 18.1 million new cases of breast cancer and
9.6 million deaths were reported in 2018. Breast cancer accounts up to 38.5% of female cancers [67].
It was also estimated that globally in next 5 years, the prevalence of breast cancer will be around
43.8 million [68]. Despite the incidence rate being low, the mortality rate of breast cancer among black
African people remains higher than 40% [69].
Cancer is mainly classified based on origin. Breast cancer is named after the breast tissue with
erratic growth and proliferation of cells. The breast is mainly composed of two different vital tissues:
stromal and glandular tissues. The stromal tissue also known as supporting tissue, which includes
fatty and fibrous connective tissues, while the glandular tissues are made up of lobules and ducts [70].
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There are many types of cancer that develop in various parts of the breast. Most of them develop
from the cells lining the ducts and the lobules [70]. These types of cancer are in situ or invasive.
The two main types of breast carcinoma in situ are ductal carcinoma and lobular carcinoma. Ductal
carcinoma in situ is known to be the precursor of invasive cancer, while lobular carcinoma in situ is a
benign condition [71].
There are various risk factors that are associated with development of breast cancer. These risk
factors including aging, family history, low parity, estrogen, and life styles such as alcohol abuse
can lead to the development of breast cancer. There have been advancements in clinical and breast
cancer related theoretical studies. However, these studies have helped in the development of breast
cancer preventive measures. Currently, breast cancer preventive measures include screening, biological
prevention, and chemoprevention [72].
The treatment and management of breast cancer is dependent on the stage and type of tumor.
The common treatment modalities for breast cancer include chemotherapy, surgery, human epidermal
growth factor receptor 2 (HER-2) directed therapy, endocrine therapy, and radiotherapy [73].
The introduction of natural plant-derived anticancer compounds has improved in the treatment
of various cancers including breast cancer. Several reviews have highlighted the benefits of naturally
derived phytochemicals as compared to the synthetic compounds. Some of the common natural
bioactive phytochemicals used in anticancer therapies are vitamin E, hydroxytyrosol, resveratrol, etc.
Apigenin is a phytochemical extracted from parsley vegetables are known to demonstrate cytotoxic
activities against colon and breast cancer cell-lines [10].
10. Lung Cancer
Lung cancer is the most common neoplasm that occurs among men and women in most
countries. The GLOBOCAN 2012 estimated a total of 1,242,000 new cases in men and 583,000 in
women. Lung cancer is histologically classified into two classes. These classes include small-cell and
non-small-cell lung cancers (NSCLC). In the United States, it was approximated that 200,000 persons
were diagnosed with lung cancer in 2010 and 160,000 deaths were reported. It is the main cause
of mortality in both men and women. Approximately 27% of cancer deaths, which was reported
in the USA during 2015 and 20% deaths reported from European Union in 2016 were due to lung
cancer [74]. Tobacco usage is the well-known risk factor that accounts for 80% to 90% of lung cancer
development [75]. There are various risk factors that are associated with the development of lung cancer.
The major risk factors include age and cigarette smoking. Cigarette smoking increased dramatically in
the United States of America and the European countries [76].
Physical examinations, radiological imaging, and biopsy tests are performed in non-small-cell lung
cancer, and the staging is based on the outcome of these investigations. Surgery can be performed in
order to determine the pathological stage of cancer by direct examination of biopsies [77]. Most medical
centers and hospitals have adopted the TNM staging system used in the staging of cancer where T is
the size of the tumor; N is the number of lymph nodes that are infected, while M refers to the level of
metastasis [78].
Therapeutic approaches to be employed in the treatment of lung cancer are dependent on the
stage of cancer. Currently lung cancer is treated by chemotherapy, immunotherapy, targeted therapy,
and radiotherapy. Although immunotherapy has made tremendous progress in the treatment and
management of lung cancer, chemotherapy is the current standard treatment to be employed in the
first and second line in the management of small-cell lung cancer (SCLC) [79]. Pre-clinical trials of
6-Shogaol, a bioactive compound extracted from ginger, have shown effectiveness in the treatment of
non-small-cell lung cancer (NSCLC). In an experimental model involving a nude mouse, 6-Shogaol
inhibited the growth of lung cancer cells. The growth inhibition of NSCLC was significantly associated
with the decreased proliferation and increased apoptosis induction [27].
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11. Colorectal Cancer
Colorectal cancer is the second cause of cancer-related death in the United States. Globally,
colorectal cancer is the third leading cause of death in both men and females. According to the
GLOBOCAN report of 2018, colorectal cancer is the fourth common diagnosed type of cancer [80].
The increasing incidence rate of colorectal cancer in developed countries can be related to risk factors
such as dietary, smoking, obesity, and age [81]. Surgery remains the primary treatment modality if
early diagnosed [82]. The introduction of plant-derived phytochemicals plays an important role in the
treatment and management of colorectal cancer. Phytochemicals of natural origin inhibit colorectal
tumor growth through pathways such as phosphoinositide 3-kinase (PI3 kinase), STAT 3, and Wnt
signaling pathway [10].
12. Prostate Cancer
Prostate cancer is one of the most commonly diagnosed cancers found in men after lung cancer.
Despite advancements in the treatment of cancer and research, prostate cancer deaths had risen to more
than 300,000 deaths worldwide. The risk factors related to one developing prostate cancer include
age and family history [83]. When compared to other countries, prostate cancer is more diagnosed in
American and European men [84]. Therapeutic approaches to be employed in the treatment prostate
cancer include chemotherapy, prostatectomy, and radiation therapy [85].
13. Scope and Importance of Dicoma in Anticancer Research
Plants are reservoirs of various phytochemicals [68]. Tumor recurrence and side effects elicited by
chemotherapy have reduced the efficacy of most of the anticancer agents. Phytochemical constituents
from D. anomala play a very important role in the development of new potent anticancer agents.
Apart from being widely used in therapeutic purposes, D. anomala extracts are also used in industries
to manufacture drugs, herbicides, and cosmetics [86]. Combination of alkaloid derivatives with other
therapeutic agents proved to be more effective in the treatment of different types of cancer [87].
14. Combination Therapies Using Plant-Derived Phytochemicals
Cancer is a global health problem that leads to increased morbidity and mortality. Therefore,
various research projects are focusing on the development of effective therapeutic approaches that
will prolong human lives. Combination of cancer therapies is aimed to reduce the possibility of drug
resistance during chemotherapy [88]. Since 4500 BC, plant extracts have been used in traditional
practices by Indian and Chinese people. Advances in analytical chemistry have improved in the
investigation of plant-derived extracts for potential medicinal components [27]. Combined therapy is
the new direction taken to fight against cancer. It has a high efficacy when compared to monotherapy
and provides an improved treatment efficacy and with minimal adverse effects [89].
15. Conclusions and Future Perspectives
Due to an increased resistance and adverse side effects exhibited by radiotherapy and
chemotherapy, plant-derived bioactive compounds are considered as a potential source of anticancer
agents with less side effects and cost effectiveness. Not only in cancer treatment, phytochemicals of
plant origin are used by most countries in the treatment of various medical conditions. Bioactive
phytochemicals are known to have anticancer, antibacterial, anti-inflammatory, antiviral, antioxidants,
and antiplasmodial properties. Therefore, more efforts are being made by researchers to explore
different plant extracts and identify the potent active principle compounds. Present research outcomes
create a baseline for the validation and standardization of plant-derived drugs. D. anomala, one of the
little-known African medicinal plants, has diversified pharmacological and phytochemical properties
that need to be subjected to a detailed evaluation with special reference to cancer.
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Due to the diversified pharmacological properties of plant-derived bioactive compounds,
many researchers are focusing on developing plant-derived products for cancer treatments. Stem cell
therapy by using plant-derived bioactive compounds and targeted biomarker development will replace
the current synthetic ones. There are many anticancer phytochemicals without a clear mechanism
of action, hence many of these compounds have to be subjected to clinical trials. Clinical trials
are important, because they help in validating efficacies and adverse effects associated with those
compounds. Combining traditional medicinal practices with modern treatments is one of the suggested
approaches in the treatment and management of various types cancer for improved effectiveness.
Author Contributions: Conceptualization and writing, A.C.; review and editing, A.C.; B.P.G. and H.A.; supervision,
B.P.G. and H.A. All authors have read and agreed to the published version of the manuscript.
Funding: This work is supported by the South African Research Chairs initiative of the Department of science
and technology and National Research Foundation of South Africa (Grant No 98337), as well as grants received
from the University of Johannesburg (URC) and the Council for Scientific and Industrial Research (CSIR)-National
Laser Centre (NLC).
Acknowledgments: The authors sincerely thank the Department of science and technology and national Research
foundation of South Africa, Laser Research Centre (LRC) and the University of Johannesburg for the support.
Conflicts of Interest: We wish to confirm that there are no known conflicts of interest associated with
this publication.
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