Alternative Remedies and Natural Products for Cancer Therapy: An Integrative Approach

“Ayurveda”, an ancient Indian science of living which originated about 5000 thousand years ago, establishes ways of living a healthy life by establishing harmony between body, mind, and spirit. Ayurveda suggests lifestyle and dietary changes for the management of cancer and cancer like symptoms. Though the occurrence of this disease about five thousand years ago was sparce, yet the ayurvedic texts do mention some symptoms that can be aliased to cancer. These are often treated by different Ayurvedic procedures and formulations. Majority of these formulations balance the elements in our body referred to as “Tridoshas” which are vatta, pitta and kapha. It has been reported that the herbs, lifestyle and dietary changes that act by balancing “Tridoshas” show beneficial effects on cancer at various stages of the disease. Medicinal plants that possess a set of defined attributes such as bitter, pungent, astringent biopotency, act as excellent candidates for prevention, mitigation and treatment of cancers. Moreover, using systems pharmacology and bioactivity-guided fractionation, it is now possible to decipher the molecular mechanism of action of these potent anti-cancer herbs. An amalgamation of Ayurvedic systems and modern medicine put together as “Modern Ayurveda” is proving efficient in cancer therapy.

Aromatherapy is a complementary healing therapy that uses aromatic essential oils to improve the health of the body and mind. Essential oils with healing properties, like geranium oil, rosemary oil, lavender oil, patchouli oil, and others, have been used to treat cancer. Cancer is often treated using chemotherapy and/or radiation therapy. Nausea and vomiting are often side effects of chemotherapy and radiotherapy. Subsequently, these cancer therapies lead to various psychological disorders, such as stress, anxiety, and depression, in cancer patients. Hence, the a need to assist cancer patients in overcoming these disorders. Aromatherapy, which is a blend of essential oils, has been reported to improve disorders that arise during complicated cancer therapies such as chemotherapy and radiation. Research on cancer populations has revealed that patients exposed to essential oils via inhaler devices had reduced anxiety, stress, nausea, and poor sleep. The effects of aromatherapy are reported to be due to the binding of chemical components in the essential oil to receptors in the olfactory bulb, impacting the brain’s emotional center, the limbic system. Aromatherapy has also been reported to relieve pain, muscular tension, and fatigue. Aromatherapy practitioners treat specific conditions using various combinations of oils and different modes of application. Aromatherapy can thus be used as a potential supplement treatment to improve complications in cancer; however, further studies are needed to estimate the protocol and standard dosage. Given the difficulties of cancer treatment, aromatherapy can play an important role in treating patients' psychological aspects. 

The immune system is amazingly complicated and vital for our survival. Several different systems and cell types of our body work effortlessly in ideal synchrony throughout the body to fight off pathogens and clear up dead cells. Our immune systems perform an implausible job by putting up a wall that can safeguard the disease-causing microorganisms. Our immune system requires equilibrium to function smoothly, so a person must eat and drink healthy balanced foods for getting energy and nutrients. The immunity related diseases may occur due to several factors such as seasonal change, environment factors, virus attacks, and simple stress. To combat these, we need to consume immunity-boosting foods and nutrients rich in antioxidants like Alium sativum, Alium cepa, Citrus limon, Withania somnifera,Moringa oleifera, Curcuma longa, etc., which can build up the immunity. The traditional system of medicine like Ayurveda and Siddha system of medicine quoted several traditional immune-boosting recipes like Maha- sudharshnachoornam, Talisadichoornam, Dhanavantam, Gulika-churnam, sitophaladichoornam, etc. Several times it is proven that lifestyle and dietary changes can result in a better immune system. A healthy lifestyle includes consuming foods which help in boosting immunity. In addition to keeping a balanced diet in our daily life, there is a necessity for traditional immunityboosting agents simultaneously. Traditional immunity-boosting agents are usually rich in vitamins, antioxidants, and other minerals and the requisite nutrients for maintaining equilibrium in the immune system. In this chapter, detailed information about Traditional immunity-boosting agents will be discussed.

India has rich biodiversity and a large number of medicinal plants that are weeds. Usually, weeds are seen as troublemakers in the yard and interfere with the man's land utilization for a specific purpose. Farmers and field botanists recognized these weeds as medicinal plants such as Adonis vernalis, Phyllanthus amarus, Eclipta alba, Centella asiatica, etc. used in folk and indigenous medicines. Most of the plants that are considered weeds have not yet explored phytochemically and pharmacologically. Simultaneously, many of these weeds were reported for their secondary metabolites like alkaloids, glycosides, flavonoids, phenolics, saponins, etc. having medicinal values like anticancer, antioxidant, and anti-inflammatory activities. Many therapeutically important weeds are more popular in India, like Achyranthes bidentata, Artemisia nilagirica, etc. with preferable medicinal benefits such as a diuretic, anti-malarial, and brain tonic. Weeds are storehouses and chemical libraries with simple to complex bioactive secondary metabolites, which serve as drug leads against several resistance diseases like cancer and tuberculosis. Weed biomolecules like Atropine from Atropa belladonna, Berberine from Berberis vulgaris, Colchicine from Colchicum autumnale, Phenoxodiol from Glycine max, Ingenol 3-angelate from Euphorbia species, Combretatin from Combre vulgaris have been reported. This chapter explains various cytotoxic Indian weed flora, reported phytochemicals, drug leads, ethnomedicinal values, modern pharmacology, mechanism of action and clinical safety and efficacy issues. 

Botanicals obtained from nature are the major source of therapeutic medicines for humans. Utilization of botanicals for a variety of diseases is not mysterious, and a rapid increase in such therapeutic substances is observed due to their efficacy and long-term safety. Cancer, as a leading cause of disease worldwide, piques the interest of researchers seeking novel anticancer agents. Till date, the major share of cancer medicines is occupied by natural products, and the drug discovery process is rapidly going on. However, traditional anticancer drug discovery is time-consuming and herculean. High-throughput screening (HTS) is a tool to make natural product library screening easy and fast. The advancement of extraction, isolation, and structure characterization of Phyto actives obtained from botanicals, provides a large number of compounds for testing via HTS. High-density well plates, a liquid handling platform, automation, and robotics allow the screening of 100,000 compounds per day. Anticancer screening of botanicals by HTS can be performed on various cancer cell lines along with molecular targets, enzyme or protein interaction assays, or the capacity of the extract to induce apoptosis. After the replication of identified extracts, further assays are performed for more precise results. HTS screening and computational methods provide speed and a high degree of sensitivity for anticancer agents and compress the time required for drug discovery. Advances in HTS technology, such as ultra-HTS and the use of 3-D cultures, will speed up the process of discovering anticancer drugs from botanicals. Advanced detection techniques for HTS assays, as well as instrumental techniques for identified lead compound separation, help to ensure that the results are neat. 

Unfortunately, we are living in a century where cancer has become an epidemic that is uncontrollable. Although the plant kingdom has been explored for cancer therapeutics due to its antimutagenic, antioxidant, antiproliferative, and alteration of the human immune system potential; these efforts are still underway due to inadequate knowledge of their biochemical mechanisms and molecular pathways. Phytochemicals exert anticancer activity due to their agonistic and antagonistic potentials on different proteins and enzymes involved in the molecular pathways of cancer. This classical phytotherapy treatment has various pitfalls, such as resistance, side effects, and a lack of target specificity. Because of the target-specificity effects, traditional phytotherapy does not distinguish tumour cells from normal cells. A multitargeted approach, in which a single phytochemical act on different points of the same signalling cascade, plays an important role in this regard. Polypharmacology, system biology, and networking pharmacology are the different terminologies to use to explain in detail the multitargeting approach. Classical phytotherapy is replaced with this multitargeted approach where different “omics” such as genomics, epigenomics, transcriptomics, proteomics, metabolomics, and various cytogenic technologies are involved. In this chapter, the various multitargeted approaches involved in cancer therapy and the phytochemicals that were prominent in cancer prevention in the 21st century have been explained. At the end of the chapter, the holistic approach to the treatment of oncology has also been emphasized. 

Currently, cancer has become one of the most dreadful diseases threatening human health. Natural plant sources play a vital role in the development of several anti-cancer drugs such as vincristine, vinblastine, vinorelbine, docetaxel, paclitaxel, camptothecin, etoposide, teniposide, etc. Various chemotherapies fail due to adverse reactions, target specificity, and drug resistance of some types of drugs. Researchers are attentive to developing drugs that overcome the problems stated above by using natural compounds that may affect multiple targets with reduced adverse effects and that are effective against several cancer types. The development of a new drug is a highly complex, expensive, and time-consuming endeavour. In the traditional drug discovery process, ending with a new medicine ready for the market can take up to 15 years and cost more than one billion dollars. Fortunately, this situation has changed with the arrival of novel approaches recently. Many new technologies and methodologies have been developed to increase the efficiency of the drug discovery process, and computational methodologies utilise the existing data to generate knowledge that affords valuable understanding for addressing current complications and guiding the further research and development of new naturally derived drugs. Consequently, the application of in silico techniques and optimization algorithms in drug discovery ventures can provide versatile solutions to understand the molecular-level interactions of chemical constituents and identify the hits. Lead optimization techniques such as ligand-based or structure-based drug design are widely used in many discovery efforts. In this chapter, we first introduce the concepts of CADD, in silico tools, etc. we then describe how this virtual screening has been successfully applied. Furthermore, we review the concept of natural product anticancer therapies and present some of the most representative examples of molecules identified through this method.

Cancer has always remained a major challenge to humanity with its rising morbidity and mortality rate making it uncontrollable. Current treatments for cancer offer limited efficacy and suffer from serious side effects. With a focus on making treatment safer and more effective, there is a need to identify novel targets and potent drugs for these targets. Recent years have witnessed significant progress in the discovery of targeted cancer therapy. On-going research in this field suggests that human topoisomerases and caspases are important molecular drug targets for anti-cancer drug development. Topoisomerases are DNA processing enzymes essentially required to maintain DNA topology during transcription, replication, recombination and chromosomal decatenation. Several new chemical classes of topoisomerase inhibitors including natural product derivatives are in clinical trials for the treatment of various human cancers. Several topoisomerase inhibitors such as topotecan, irinotecan, camptothecin, teniposide and doxorubicin are clinically approved for various cancers such as colon cancer, lung cancer, breast cancer, and many more. However, many of these inhibitors have also been associated with serious side effects during chemotherapy. Emerging data in recent years also suggests the role of topoisomerase inhibition in immunogenic cell death and activating anticancer immune responses making them potential combinatorial modalities for cancer immunotherapy. Caspases [1-12] belong to the family of cysteine-aspartic proteases responsible for the execution of cell death in apoptotic cells. Caspases play an important role in various non-lethal biological processes like cell proliferation, cell differentiation, intercellular communication, and cell migration. The dysregulation of apoptotic signalling pathways is considered one of the hallmarks of cancer. Hence the focus of cancer therapy is correcting this aberrant behaviour. Natural products such as alkaloids, flavonoids, diterpenoids, sesquiterpenes, and polyphenolics have been reported with various anticancer properties. In this chapter, we have discussed topoisomerases and the regulation of caspase functions through direct or indirect methods for anticancer drug discovery. 

Cancer is a collective term for a group of deadly diseases that can affect and spread to various parts of the body. The main feature of cancer is the uncontrolled growth of cells due to a defect in the genes that control normal cell division and growth. As per the latest statistics, cancer is the second-leading cause of death globally, and almost 70% of these deaths are reported in low- and middle-income countries. Chemotherapy and irradiation are the most common cancer treatments; however, the development of resistance and severe side effects are the stumbling blocks of these methods. Hence, current research has focused more on developing novel drug leads from new sources like algae and fungi. Fungi, such as mushrooms, are an inexhaustible source of various anticancer biomolecules, and the 21st century saw a staggering interest in the anticancer potential of mushrooms among the western exploration clique. Their cellular and humoral immunity-boosting properties have made them better candidates for anticancer drug discovery. The mushrooms attributed with cytotoxic potential belong to various genera like Vargenus Agrocybe, Amanita, Antrodia, Agaricus, Albatrellus Conocybe, Clitocybe, Cordyceps, Clavatia, Flammulina, Funlia, Fomes, Galerina, Gymnopilus, Ganoderma, Hypholoma, Inonotus, Inocybe, Lentinula, Lactarius, Panaeolus, Psilocybe, Plerurotus, Pholiotina, Pluteus, Russula, Suillus, Schizophyllum, Trametes, Xerocomus, and Weraroa. Hence, the current chapter focuses on the botanical description, phytochemistry, mechanism of action, and clinical status of various vital mushrooms acting as essential libraries of anticancer drug leads.

Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. It is one of the major causes of human death, especially in developing countries. Alternative cancer treatments using medicinal plants are exploited because plants produce phytochemical compounds, which are secondary metabolites used for natural defence but could also be useful in inhibiting cancer growth. Medicinal plants also have limited side effects and toxicity as compared to conventional chemotherapy and irradiation treatments. Hence there is a need to develop novel drugs from other sources like plants, fungi, and algae. Spirulina is a blue-green alga with three species: Spirulina platensis, Spirulina fusiformis, and Spirulina maxima. Spirulina platensis and Spirulina maxima are consumable by humans in the form of dietary supplements, as they are enriched with important nutrients and a library of phytochemicals that can improve immunity and levels of blood lipids, lower blood sugar and blood pressure, and prevent oxidation. These activities of Spirulina phytochemicals make them a good candidate for anticancer therapy. Therefore, this chapter describes the botanical classification, phytochemical composition, and anticancer characteristics of Spirulina and with a specific focus on Spirulina platensis.

Cancer remains the most devastating disease that threatens public health with increasing incidence year by year worldwide. The anti-cancer property of naturally derived compounds appears to be a promising approach in cancer therapy. Terpenoids, generally known as terpenes, belong to the most abundant secondary metabolites class and extensively occur in various medicinal plants, fruits, and vegetables. Most of the terpenoids are non-toxic in nature and a ubiquitous part of the human diet. To date, approximately 50,000 terpenoids have been known in nature, and most of them have their use in traditional as well as modern medicinal systems. Based on the number of cyclic structures, terpenoids have been classified into eight main classes such as hemiterpenoids, monoterpenoids, sesquiterpenoids, diterpenoids, sesterterpenoids, triterpenoids, tetraterpenoids, and polyterpenoids. Terpenoids have shown several biological and pharmaceutical significances, including anticancer activity. The literature study revealed that terpenoids exhibit anticancer activity against various human cancers via inhibiting the initiation and progression of tumor growth in vitro and in vivo. In addition, many terpenoids inhibit cell proliferation, invasion, metastasis, and angiogenesis which promote apoptosis of various cancer cells via inhibiting various deregulated oncogenic intracellular signaling pathways. Moreover, the pre-clinical anticancer efficacy of terpenoids supports their clinical application as an anticancer therapeutic. This chapter attempts to provide a comprehensive overview of recent advancements and mechanistic progress on terpenoids as cancer therapeutic

Globally, the prevalence of cancer has escalated at an alarming rate, and it has become a major health problem. The World Health Organization reported that one in six deaths is due to cancer. Despite the advantages of current chemotherapy available for cancer treatment, the development of resistance and severe side effects continuously insist cancer research focus on the discovery of new entities, especially from natural sources. In the last few decades, varieties of dietary herbs have been explored for their cytotoxic potential. Rosmarinus officinalis, a well-known culinary herb commonly known as rosemary, is not only used to enhance the flavour but also possesses medicinal values. The Rosmarinus officinalis plant extract and its essential oil are packed with different phenolic acids and terpenoids. Rosmarinus officinalis has anti-cancer, anti-proliferative, protective, anti-inflammatory, and anti-oxidant properties, according to several in vitro and in vivo studies. The antitumor activity of Rosmarinus officinalis is correlated with different molecular mechanisms such as reactive oxygen species scavenging, the on-co-suppressor gene expression, apoptosis, and immunomodulatory response regulation. So this chapter mainly focuses on the cytotoxic activities of Rosmarinus officinalis and the molecular mechanisms responsible for their anticancer activities. Also, possibilities of utilising the extracts, essential oils, and phytochemicals of Rosmarinus officinalis as potential therapeutic agents or complementary therapies with chemotherapeutic agents for cancer treatment have been discussed. 

Cannabis has been used as a drug for centuries, possibly much longer before it was recognised as an illegal substance. The prime psychoactive property is marked on the 9-THC compound. The cannabinoids replicate the action of endocannabinoids by stimulating receptors in the central nervous system and lymphatic system via diligent CB1 and CB2, respectively. Cannabinoids, on the other hand, are well known for their dependency, which is less severe than that of other drugs that can be abused. Cannabis' anti-tumor and anti-cancer potential was only discovered at the turn of the twentieth century. Cannabis consumption has been reported to benefit patients with cancer by suppressing nausea, curbing vomiting, elevating appetite, alleviating pain, and pacifying anxiety. Studies envisage that the up-regulation of CB receptors and their associated endogenous ligands correlates with the suppression of tumours. Patients have found cannabis to be effective in reducing side effects and relieving pain when used in conjunction with chemotherapy. Though cannabis prescription is restricted under federal laws in many countries, its lucrative efficacy profile has pushed regulators to reconsider its use in medical causes such as cancer. This chapter is an attempt to emphasise the biological role of cannabis in cancer pathophysiology

Cancer has become one of the leading causes of human morbidity and mortality worldwide. A promising approach to tumour prevention is to eliminate cancer cells, preferably with less harm to neighbouring normal cells. Due to the disadvantages associated with current chemotherapy and radiation therapy, there is an increasing interest in developing novel delivery strategies for these natural products. Many phytochemicals show promise in cancer prevention and treatment due to their biocompatibility, low cytotoxicity, low resistance, and dynamic physiochemical properties that discriminate normal cells in the treatment of various cancer types. However, their low aqueous solubility, poor stability, unfavourable bioavailability, and low target specificity make their administration at therapeutic doses unrealistic. Recently developed nanotechnology has transformed drug delivery concepts and paved the way for the development of phytochemical-loaded nanoparticles for cancer prevention and treatment. Polymeric nanoparticles, lipid nanoparticles, carbon-based nanoparticles, and cell-derived nanoparticles can increase the stability and solubility of phytochemicals and also help in overcoming the disadvantages associated with conventional chemotherapy and phytochemicals. In the current chapter, we have mentioned the importance of nanotechnology in the delivery of phytochemicals and also added a note on the significance of delivery with current chemotherapeutics, including present challenges and future perspectives.