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cancers of thymus, liver, pancreas, colon, lung, breast, bone, and pancreas (Danciu, 2015).
Human colon cancer LS-174-T cells showed apoptosis induction by Curcuma longa
aqueous extract (Brockmueller et al., 2023) (Figure 6.13). Ozaki et al. (2000) discovered
curcumin’s ability to prevent bone resorption and to induce apoptosis in rabbit osteoclasts.
Curcumin promotes apoptosis in a variety of cell types, including leukemic Jurkat, COLO
205, human lung cancer A549, murine myelomonocytic leukemia WEHI-3, human nasopharyngeal carcinoma cells, and NPC-TW 076.
FIGURE 6.13 Mechanism of anticancer activity of Curcuma longa.
⏎
6.4.2 VISCUM ALBUM L.
V. album, an evergreen shrub also referred to as mistletoe or European mistletoe, belongs
to the Santalaceae family (Adeneye, 2014). It is extensively found in central Asia,
southwest and northwest Africa, and Europe. V. album serves as a plentiful reservoir of
various compounds, including flavonoids, phenylpropanoids, alkaloids, proteins, carbohydrates, oligosaccharides, polysaccharides, triterpenes, steroids, lipophilic molecules,
viscumneoside XII, XIII, XIV, lectins, viscotoxins, and conjugated acetylene compounds.
Urech
et al. (2006) reported the anticancer properties of lectins and viscotoxins present
in V. album. According to the reports, V. album have biological properties that include
hepatoprotective, antidiabetic, antioxidant, anti-inflammatory, sedative, and anticancer
effects (Stefanucci et al., 2020).
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Compounds extracted from this V. album such as viscotoxin, viscumamidines demon-
strated direct antitumor efcacy in mice.
6.4.3 COLCHICUM AUTUMNALE L.
The blooming plant C. autumnale, majorly known as the “autumn crocus,” is a member of
the Colchicaceae family. It is indigenous to Ireland and Great Britain. Due to the presence
of an alkaloid, colchicine, in the corms, C. autumnale is regarded as a dangerous plant
(Akhbar, 2020). Colchicine has a various therapeutic use as it is used to treat gout, Behçet’ s
illness, and familial Mediterranean fever. Colchicine’s pain-relieving, anti-inflammatory,
and antiproliferative effects are closely linked to its ability to interact with tubulin, a critical
component involved in cell division.
Colchicine inhibits the function of tubulin at the G2/M phase of the cell cycle, severely
damaging the internal architecture of the cells and inducing apoptosis. Colchicine has not
been utilized extensively in the treatment of cancer due to its severe toxicity, although it is
nevertheless employed as a lead molecule for the development of prospective anticancer
medicines.
6.4.4 RAPHANUS SATIVUS L.
Raphanus sativus, a member of the Cruciferae family , is a significant and traditional annual
vegetable. Compounds extracted from R. sativus such as glucosinolates and isothiocyanates controlled the phase I and phase II detoxification systems, greatly limiting the growth
of HepG-2 cells. The glucosinolate chemicals 4-methylthio-3-butenyl isothiocyanate and
glucoraphasatin found in R. sativus extract are responsible for its anticancer properties
(Khazir, 2014). R. sativus extracts demonstrated efficient cytotoxicity against the HCT116
colon cancer cell lines by triggering apoptosis. The extract of aerial plant parts also showed
excellent cytotoxicity in the MDA-MB-231 breast cancer cell line through the ErbB-Akt
pathway, which means they had the ability to cause cell death in these specific cancer
cells. ErbB-Akt pathway comprises of ErbB family of cell surface receptors, also known
as epidermal growth factor receptors, which are involved in cell signaling and regulation
of cell growth, proliferation, and survival. The ErbB pathway is critical in many cellular
processes, including cancer development and progression. Abnormalities in this pathway
are commonly associated with various types of cancer, including breast cancer . Akt (protein
kinase B): Akt, also known as protein kinase B, is an important downstream component of
the ErbB pathway. Activation of Akt is often associated with enhanced cell survival and
resistance to cell death signals.
6.4.5 TINOSPORA CORDIFOLIA WILD
The herbaceous vine T. cordifolia is a member of the Menispermaceae family. It is a
native of the Indian subcontinent's tropical areas. It is used as an immunostimulant and to
125
treat diabetes, rheumatoid arthritis, and jaundice in Indian Ayurveda medicine. The antineoplastic, antioxidant, hepatoprotective, hypolipidemic, and immunologic activities of T.
cordifolia are well recognized (Nathe, 2023). T. cordifolia contains a variety of bioactive
compounds, including diterpenoids, polysaccharides, lactones, aliphatic compounds,
steroids, alkaloids, sesquiterpenoids, and glycosides. Because of its antiperiodic, antispasmodic, antibacterial, antiosteoporotic, anti-inflammatory, antiarthritic, antiallergic, and
antidiabetic activities, T. cordifolia extract is widely utilized in pharmaceutical formula-
tions. T. cordifolia is known to counteract the toxicity caused by cyclophosphamide in
cancer (Akash et al., 2022).
6.4.6 NIGELLA SATIVA L.
Nigella sativa belonging to the Ranunculaceae family, is indigenous to Eastern Europe
and Western Asia, and has an annual blooming cycle (Rafati et al., 2019). Thymoquinone
is the primary bioactive substance of N. sativa that exhibits anticancer effects (Figure
6.14). Thymoquinone causes death of aberrant cells while exhibiting growth-inhibitory
properties. According to Gali-Muhtasib et al. (2008), thymoquinone reportedly inhibited
tumor development in mouse models. Rafati (2019) reported that topical administration
of N. sativa gel lessens the severity of acute radiation dermatitis among breast cancer
patients. Moreover, it has been shown that consuming N. sativa seeds orally reduced
febrile neutropenia in kids with brain tumors (Fadel, 2017). Thymoquinone affects the
phosphorylation process of signaling pathways and the activation of several tyrosine kinases
(e.g., PIP3, mTOR, Akt, and mitogen-activated protein kinase), which play crucial roles in
the proliferation of tumor cells. Additionally, thymoquinone regulates various tumorigenic
processes, including cell survival, proliferation, invasion, inflammation, angiogenesis, and
metastasis. Moreover, it influences the activation of transcriptional factors like NF-kB,
Nrf2, and STAT-3. Thymoquinone exhibits chemopreventive properties by reducing the
production of proinflammatory mediators (e.g., prostaglandins, chemokines, and cytokines),
upregulating the cytoprotective enzymes (e.g., oxidoreductase, superoxide dismutase, and
glutathione S-transferase), and downregulating the carcinogen metabolizing enzymes (e.g.,
CYP 3A4 and CYP 1A2).
6.5 THERAPEUTIC ENZYMES
l-asparaginase, l-glutaminase, l-argininase, and l-methioninase are some examples
of enzymes that are used in cancer therapy, which target specific amino acids resulting
in the disturbance of cancer cell proliferation without affecting normal cell metabolism.
During tumorigenesis and metastasis, oncogene activation and oncosuppressor inactivation lead to a rewiring of cancer cell metabolism. This alteration drives the cells toward
new cellular homeostasis, primarily focused on anabolism, facilitating the rapid growth
and proliferation of cancer cells (Maggi and Scotti, 2019). Amino acid deprivation therapy
(AADT) is emerging as a promising strategy for the development of novel therapeutics
126
against cancer. This biological therapy relies upon the differences in the metabolism of
cancer and normal cells. The enzymes used in AADT are mostly obtained from microbes
for their easy availability. Microbial l-asparaginase is already approved by the FDA for
the treatment of ALL. ADI1 and methionase are under clinical trials and the therapeutic
potential of lysine oxidase, glutaminase, and phenylalanine ammonia lyase is also being
explored. Therapeutic enzymes like superoxide dismutase, tyrosine phosphatase have also
been reported as novel potential candidates for drug development against cancer (Kambaru
and Chaudhary, 2021; Saxena et al., 2021; Selvaraj et al., 2021; Roy et al., 2022).
FIGURE 6.14 Compounds derived from Nigella sativa.
⏎
6.6 FUTURE PERSPECTIVE
Drugs derived from natural products are highly sought after because they are no
more toxic to healthy cells and have cytotoxic effects on cancer cells. The commerce
in medications derived from plants was valued at $100 billion in 2007, according to
the WHO. By 2050, it is anticipated that commerce will value a total of $5 trillion
USD. The growing strain on plant populations is caused by the enormous demand for
therapeutic herbs in emerging nations. High-value medicinal plants face the threat of
extinction as a result of increasing demand and ongoing overexploitation. To ensure
their survival, it is essential to adopt sustainable harvesting practices. Removing only
specific portions of a plant, such as its roots, stems, leaves, or flowers, without allowing
adequate time for regeneration can harm and reduce the plant’s ability to survive and
propagate, putting its long-term existence at risk. Proper management and conservation
127
efforts are vital to protect these valuable plant species for future generations. Currently,
in clinical trials, ixabepilone and UTD1 are used in addition to traditional antitumoral
medications to enhance cancer treatment and improve patient prognosis (Villegas et al.,
2023). The enzyme l-asparaginase, derived from Rhodospirillum rubrum (RrA), facilitates the hydrolysis of l-asparagine to produce l-aspartic acid. Due to the limited efficacy of current l-asparaginases from E. coli (EcA) and Erwinia chrysanthemi (ErA),
RrA has emerged as a potential and novel treatment for leukemia. By modifying RrA
with polyamines, enzyme preparations with enhanced biocatalytic capabilities have
been developed. These conjugates hold promise for further investigation as possible
medicinal agents (Dobryakova et al., 2023). Salmonella typhimurium is another type of
bacteria that has been modified to target cancer cells and is presently being evaluated in
clinical trials for different types of cancer.
6.7 CONCLUSION
In both developed and underdeveloped nations, the problem of cancer is increasing at
an alarming rate, and there is a huge need for cancer treatment and prevention. Cancer
therapies are available, for example, chemotherapy, but it has harmful effects on tissues
that are not its target, aggravating human health conditions. As a result, there is a demand
for complementary therapies that use naturally occurring anticancer chemicals, with plants
as the preferred source. Plant-derived anticancer substances are in great demand as they
effectively suppress cancer cell line growth. To meet demand and remain sustainable, the
exploitation of these agents needs to be regulated. Novel pharmacophores, chemotypes,
and numerous medicinal compounds can all be found in nature, which is an endlessly
renewable resource. Many contemporary medications have been created from organic
materials. Around 50% of the medicines that have been approved come from natural
sources. Microorganisms such as bacteria and fungi produce natural products that can
be categorized as both primary and secondary metabolites, and many of these have been
approved by the FDA. Thus, it is imperative to state that natural compounds from both the
sources, plants and microbes, seem to be promising candidates against cancer with future
potential for drug development.
KEYWORDS
• cancer
• plant-based compounds
• microorganisms
• anticancer property
• natural products
128
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