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This book aims to fill research gaps in the search for chemotherapeutic and chemopreventive natural compounds. It includes a collection of detailed reviews focusing on bioactive compounds from plant sources that can be beneficial for cancer therapy. Topics covered include the role of antioxidants in cancer therapy, medicinal plants for cancer chemotherapeutics, bioactive compounds from marine plants, and a review of inhibiting nitric oxide reactions for preventing cancer. Chapters are contributed by researchers who have provided detailed lists and descriptions of the relevant plant sources, the compounds and the biochemical reactions. The book includes references for advanced reading. This book is intended as a reference for scholars and healthcare professionals studying natural medicines for cancer prevention and treatment.
Readership
Scholars in the field of medicinal chemistry, pharmacology and herbal medicine.
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Seitenzahl: 293
Veröffentlichungsjahr: 2024
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Research on medicinal plants is one of the most important areas in oncology with high potential in the design and development of cost-effective drugs. Natural products in the treatment of diseases have been practiced since ancient times. Cancer chemoprevention is a broad term that uses synthetic and natural compounds to slow down, suppress or reverse carcinogenesis. The onset of cancer depends on various factors such as intrinsic and extrinsic. Natural therapies, such as the use of plant-derived products and medicinal plant extracts in cancer treatment, may reduce the adverse side effects of conventional treatments. The cancer control measures are related to the origin and risk factors. Every cancer type needs specialized therapy, and the most important treatment goal is to eradicate tumour and prolong the patients’ lifespan. Alternative therapies have been playing a crucial role in cancer treatment and management. Several studies reported that medicinal plants and bioactive compounds from plants can work well as an alternative cancer treatment option for different types of cancers due to fewer side effects and cost-effectiveness compared to many existing treatments. Phytochemicals from medicinal plants were reported to reduce various risk factors associated with cancer through their chemopreventive action. This book highlights the role of bioactive compounds and dietary factors or natural products from plants or medicinal plant extracts in the chemoprevention of various types of cancer. Since the role of antioxidants in chemoprevention is unavoidable, an insight into plant-based antioxidant compounds that fight against cancer is also discussed in this book. Medicinal plants, bioactive compounds derived from marine sources, and the role of antioxidants in cancer therapy and chemoprevention, and molecular mechanisms in clinical trials are included in this book. This will fill the research gap in search of chemopreventive natural compounds and encourage researchers to produce anticancer agents from plants in clinical trials.
Malignant diseases have been highlighted as one of the most prominent causes of human mortality worldwide. The prevalence of cancer is constantly increasing and is expected to reach three-fourths of the population in the next two decades. Conventional cancer treatment involves surgery, controlling and reducing the growth of cancer tissues using radiation, and chemotherapy. Many incidences prove that chemical treatment for cancer is immensely associated with the recurrence of cancer, and the development of resistance, and is prone to severe side effects. Since natural products have now been used in the treatment of various diseases, the anticancer properties of natural drugs and druggable products are interceded by various mechanisms, including the initiation of programmed cell death, modulations in the immune system, and inhibition of angiogenesis. Edible, medicinal plants and spices used in traditional medicine to regulate vital molecular targets are important chemo-preventive agents in the treatment of chemo and radiation therapy-induced toxicities in drug development. Natural agents could trigger cell death signalling pathways in tumour cells by stimulating anti-apoptotic proteins and/or overcoming pro-apoptotic proteins and caspases. It inhibit protein kinase B (Akt), phosphatidylinositide 3-kinases (PI3K), epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK), as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Bax/Bcl-2 ratio changes, inhibiting cellular proliferation, and differentiation, and also activating apoptosis lead to less prominence. To summarize, this chapter highlights the current status, and forthcoming prospects of cancer treatment and prevention as well as the potential of bioactive compounds that have been used in cancer treatment and chemoprevention.
Cancer is a life-threatening disease and a prominent cause of death globally [1], and is probable to rise in the next 2 decades. Generally, it is assessed that the total
cancer prevalence could extend up to 2.84 crore in 2040 [2]. Oxidative stress induced by free radicals is usually found in physiological and metabolic processes and the human body has a defensive system of antioxidant mechanisms; these include enzymatic antioxidants e.g., superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) as well as natural antioxidants such as vitamins, carotenoids, polyphenols, and other antioxidants, which have the potential to neutralize free radicals [3]. Henceforth, research has been directed towards therapeutic plants and the promising potential of such plants in various traditional and alternative medicine systems for use in humans has been valued. The secondary metabolites are measured as good chemopreventive agents and can be used for cancer therapy due to the high concentration and a wide variety of natural antioxidants such as resveratrol, vitamins, flavonoids, polyphenols, and other compounds found to influence different cancer cells both in vitro and in vivo. As an antioxidant network, these natural antioxidants also have efficient synergistic interactions and renewing prospects [4]. Though huge advances have been made in research focusing on the etiology and molecular substructures of cancer, the treatment for cancer has severe side effects that limit patients’ quality of life.
Hence, it is a matter of life and death to intend processes to diminish cancer occurrence or inhibit the development of cancer to its advanced stage. The knowledge of chemical prevention is acquired with more concern comparatively due to its success in reducing the frequency of metabolic disorders and heart diseases.
Chemo preventives can be classified based on the point at which they perform as primary, secondary, and tertiary groups. Primary chemopreventive are aimed at suppressing the incidence of cancer formation in a predisposed metabolism. Secondary chemical prevention agents overwhelm the evolution of cancer prevalence from non-dangerous (benign) to dangerous (malignant). Tertiary chemical prevention agents lower the risk of tumour reappearance following a suitable treatment like incision and/or chemotherapy [2]. Among several kinds of cancer chemo preventive agents, hormonal and vaccines are recorded as more promising means for future research and therapeutics. In addition, individuals who have benefitted from chemical prevention due to their hereditary advantages give diverse interpretations for the efficient assessment of cancer chemotherapy [5].
The metabolic trembling molecules acknowledged as free radicals have damaged the other molecules. In presence of oxidative stress, these free radicals develop cancer and a chain of reactive oxygen species. Antioxidants play a vital role in plants' and animals’ nutrition because they react with these free radicals, which soothe and quench them. Natural antioxidants from plants including vitamins C, E, and A, curcumin, beta-carotene, kaempferol, and quercetin assure that the systematic intake of fruits and vegetables has consistently reduced not only the risk of cancer incidence but also other diseases like Cardiovascular disease, Diabetes, Alzheimer's disease, etc. [6].
In recent years, neoplasm medicine research has taken significant steps towards additional efficiency, specifically invasive cancer treatments. Nanomedicine combined with directed treatment aided in recovering the bio-distribution of novel or existing chemotherapeutic agents. Other approaches like gene therapy, siRNA delivery, immunotherapy, and antioxidant supplements provide new prospects for malignancy victims. In contrast, hyperthermal or hypothermal treatments are favourable substitutes and personalised medicine for tumour excision. Additionally, recent radiomics and pathomics methods for the management of big data sets from cancer patients to recover and predict cancer recurrence and related effects on their health [7].
Most of the novel therapies, including nanomedicine are flexible and safe for the living tissues and environment and can deliver chemotherapeutic drugs that can also be used with diverse applications from diagnosis to treatment [8]. Extracellular vesicles play a significant role in apoptosis and are explored as a proficient remedy in cancer therapy. Plant-derived antioxidants and numerous bioactive compounds have been recently used as adjuvant cancer treatments with pro-apoptotic properties. Gene therapy targets genes that trigger cancer suppressors and tumor suppressors that have been valued and tested in many clinical trials worldwide [9]. These approaches are the best-adapted treatments for cancer sufferers and the prominence of multi-disciplinary approaches to attain the desirable effects as proved in various clinical experiments. Cancer treatments and newly anticipated approaches that are in the investigation phase should overcome the constraints of cancer. Diverse strategies for cancer diagnosis, treatment and addressing existing consequences from the scientific perspectives and causal impacts of natural agents are required to approach the disease closer [10]. Though much debate has arisen about the efficiency of cancer chemotherapy, inadequate substantiation has been observed in both the quality and dose of antioxidants, which suggests that they may reduce antagonistic responses and harmfulness [11]. It is indicated that researchers’ effort to explore alternate composition and treatment methods to reduce persistence, growth and multiplication, transference of cancer cells, and development of blood vessels [12] and the interface of chemical treatment and antioxidants is more complicated than merely preventing oxidative stress. However, there are numerous multifaceted mechanisms in the metabolic process, which is an acceptable truth.
Each antioxidant has diverse role in chemotherapy and these influences can be adjusted based on the dose. In research on the role of antioxidants in cancer therapy, two doses of antioxidants are used as preventive dose (low dose) and therapeutic dose (high dose). Evidently, many research outputs imply that low doses of antioxidants guard normal cells and avoid tumor prevalence, whereas high doses halt the growth of cancer cells but not normal cells [13]. Certain recent reviews on natural agents concluded that antioxidants, when given simultaneously with cancer therapy denied to interact with chemical drugs at treatment; furthermore, they increase the chemical drug efficiency and body’s reaction to the drug, act as a shield for unaffected cells, and increase the patient’s quality of life [14, 15].
According to food composition data, we consume considerable amounts of anthocyanins, including delphinidin and malvidin, which can be obtained from fruits and vegetables. These anthocyanins are aglycones with a polyphenolic ring structure [16].
The consequences of reactive nitrogen species (RNS) and reactive oxygen species (ROS) leads to impairment in the cellular membrane and interfering biomolecules like amino acids and DNA; by this means, stimulating sequences of reactions are the sources of gene mutations and abnormal gene/protein expressions. Cancer stimulation or development, also known as carcinogenesis, is one of the processes that relate metabolism to various other factors [17]. This view emphasizes that scientific cancer research focuses on the concept of nutritional facilitation in order to prevent and suppress any efficient molecular target. The natural compounds from plant sources obstruct cancer stimulation by either of the predicted pathways.
According to Wattenberg in 1985, all kinds of chemopreventive agents are either inhibitors of carcinogen development, blocking or suppressing agents, or combinations of the above two or more. The agents may prevent cancer-triggering substance formation from the precursors or avoid mutations by hindering particular metabolic pathways or purification methods by scavenging ROS. Ultimately, it prevents cancer cell proliferation through apoptosis, autophagy, and necrosis stimulation [18].
As a boon of nature, natural antioxidants like flavonoids, alkaloids, and phenolic acids may trigger pathways in cancer cells to death by playing more than one role in the course of free radical balance, antioxidants in normal cells, triggering apoptosis in cancer cells, activating and suppressing anti-apoptotic protein, pro-apoptotic protein and down-regulating pro-inflammatory signalling pathways. These antioxidants suppress cancer cell proliferation by inhibiting protein kinases of cellular metabolism [19-21].
After absorption, natural compounds undergo assimilation and chemical transformations like methylation, sulfation, or glucuronidation before they get into the bloodstream where they interact with the tissues. Natural chemical residues in the proximal intestine are digested further by microbes in the colon where microbial enzymes break down the complex heterocyclic ring into hydroxylated phenyl carboxylic acids. This simple form of chemical could be absorbed in the gastrointestinal tract in succeeding phases (Fig. 1) [22].
Fig. (1)) Natural compounds (Flavonoids) targets apoptosis pathway [22].Natural agents could accelerate estrogen receptor-α (ER-α) expression and change two cytoplasmic proteins, B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and Bcl-2 ratio which control the proliferation of cancer cells followed by differentiation and also prompting a programmed cell death process in cancer cells [23]. Condition of suppressed Bcl-2, Bcl-xL protein family controls cell death by the effects of C-inhibitor of apoptosis protein 1 (c-IAP1), survivin protein, and NF-κB in ovarian cancer cell lines (C200 and A2780) [24]. An amplified caspase-3 activity [25] and stimulated the intrinsic apoptotic signalling pathway led to the activation of caspases 7 and 9 and also changed the ratio of Bax/Bcl-2. Induction and reduction of anti-apoptotic protein expressions, resulting in mitochondrial cytochrome C release cause further stimulation and follow the apoptotic pathway linking caspases 3 and 9 [26].
Similarly, p53 protein stimulation by overexpression of oncogenes, heat shock, DNA damage, and hypoxia. Due to its function in cell fate results after stimulation, directing pathways aid in sustaining genome stability and thus providing shelter to the DNA against mutations that cause cancer [27]. Experiments proved to induce cell death via improved p53 expression, Bak, Bax, and caspase-3 cleaving, and reduced Bcl-2 expressions [28, 29].
Though, caspases are either initiators or effectors in the apoptosis process, all caspases are structurally similar [30]. The second mitochondrial activator of caspases (SMAC) endorses caspase stimulation in the cytochrome C/APAF-1/caspase-9 pathway. Here, SMAC clings to inhibitors of apoptosis proteins (IAPs), which stimulate caspase-9 activation and terminate their inhibitory activity [31].
Thus, novel natural drugs with rich antioxidant capability could target death receptor (DR)-mediated (extrinsic) and mitochondrial-mediated (intrinsic) pathways in metabolism which downregulate PI3K, Akt, and Bcl-2, BCL-xL proteins led to apoptosis in the cell cycle [32, 33].
The efficiency of cancer therapeutic medications is successful but mostly limited to numerous harmful side effects. Hence, to reduce these side effects, antioxidant supplementation is frequently required to minimize ROS levels and harm. Thus, antioxidant supplementation could lessen side effects and inhibit the growth of cancer cells whereas shielding normal cells with a mixture of antioxidants along with chemotherapeutics delays further cancer development, checks chemo-resistance by refining the response to chemotherapy drugs, and improves cancer patients’ quality of life. Preclinical and clinical studies explored the efficacy of phytochemical and dietary antioxidants from different sources in the treatment of chemo and radiation therapy-induced toxicities and for the enhancement of cancer management efficacy. Besides higher taxonomic plant compounds, algae (both micro and macro) can be considered as alternative natural sources of antioxidants. Though there is enough knowledge on nutritional sources and benefits, the exploration and consumption of antioxidants, dosage, and limitations are still in their initial stages [34].
Cancer chemoprevention has been used as one or more pharmacologically dynamic agents that are proficient in blocking, suppressing, preventing, or reversing the development of invasive cancer. Exploitation of the chemical diversity of natural compounds may enrich the adept amalgams for cancer chemotherapy and chemoprevention. The new approaches and distinct clinical trials are indispensable and necessary be directed toward achieving nontoxic and effective antioxidant supplement coordination in cancer treatment. Similarly, more focused and broad research is needed to explore alternate antioxidant molecules from different sources and their extraction, purification procedures and examinations of animal metabolism are to be highlighted. Considering the several unprocessed organic and aqueous extracts with tremendous antioxidant ability along with biological properties that also have anticancer effects, scrutinizing their mechanisms of action in metabolism and their competence to potentiate chemotherapeutic drugs is a need of the hour.
Cancer is identified as the second-most deadly disease all over the world. Various advancements have been made in the treatment of cancer to protect the life of human beings. However, the side effects may destroy the lives of the patients. Economically poor patients cannot afford the treatment, and they live short lives with cancer. So nowadays, research is going on to search for drugs without any side effects and that are cheap with good efficacy. Some medicinal plants have a lot of potential to act as anticancer agents but are not medically proven as discussed in this chapter. This review will focus on the various plant-derived chemical compounds that have shown anticancer activity.
Cells are the basic and small units involved in the construction of our body. The regular activity of a cell is to grow itself, and after sometime, it will fracture or break itself. This process is known as cell replication. When this regular activity becomes abnormal, it results in cancer. These types of abnormalities are inferred due to repaired DNA in the cells. There are many ways to affect the DNA of cells. Environmental activities can damage the cellular DNA. During cell growth and replication, there will be a chance to cumulate and form tumours. In this way, tumours degrade or damage the nearby healthy cells [1].
Cancer is considered the second-most deadly disease. The main reason for cellular DNA damage is lifestyle change, which is why researchers are focusing on finding new chemotherapeutic agents that are economically favourable to society. According to the survey report given by the WHO, in 2012, only 6 million people recovered from cancer out of 14 million. This is the financial barrier faced by the
affected people [2