Name of published (Chapter): A Glance at the Effects of Secondary Metabolites in Fighting Cancer
Name of authors: Alaa Abuodeh, Leedia Abuelshayeb, Rajaa dagash, Kamel Jaber, , Areej M. Jaber, Manal Ayyash, Aya dagash, Wamidh H Talib
Abstract:
Cancer is one of the top causes of morbidity and mortality globally. Cancer is a disease of unregulated cell growth that invades and spreads to other cells and tissues. Chemotherapy of cancer has many challenges due to the low selectivity, poor water solubility, instability of molecules, and development of resistance against them. Plant-derived natural products exhibit numerous biological activities with unique mechanisms of action, making them attractive for drug development for the management of chronic human diseases, including cancer. Natural products are considered potential cancer therapies either alone or in combination with conventional anticancer medications. Most natural products exhibit own pleiotropic effects when affecting cancer cells and modulating several signal transduction and modulators, in addition to their unique structures. The goal of our study was to elucidate the mechanisms of action of several secondary metabolites’ classes on different aspects of the carcinogenesis process. We reviewed the pharmacological actions and molecular targets of the secondary metabolites. Furthermore, we emphasized the influence of secondary metabolites and conventional anticancer drug combinations on several cancer types to understand the mechanisms and advantages underlying these combinations. Plant-derived natural products fight cancer through different strategies, including apoptosis induction strategy through DNA damage and caspase activation. The antiproliferative strategy inhibits the mitogen-activated protein kinase (MAPK) pathway, immunomodulation, and anti-inflammatory activities. The other strategies target altered metabolism and tumor microenvironment, as well as inhibition of angiogenesis and metastasis. Recently, a novel practice, so-called combinatorial therapy, has been investigated by engaging plant-derived natural substances with conventional chemotherapeutics. It has been reported that plant metabolites may fortify the drug’s effective concentration, pile on the collective effect of both administered therapeutics, or increase the selectivity to tumor cells. Moreover, by steering numerous signaling pathways, combinatorial therapy uses several mechanisms to diminish the development of resistance to antitumor drugs. The interaction between plant-derived natural compounds and conventional chemotherapeutics initiates a new aspect in the research and therapy of cancer. It could be a gifted approach to treat cancer and gain fruitful improvements while diminishing adverse effects associated with conventional anticancer medications. The most studied phytochemicals include curcumin, epigallocatechin gallate, and resveratrol. Among the most investigated chemotherapeutics were 5-fluorouracil, doxorubicin, and cisplatin. A better understanding of the multifaceted mechanisms of action of phytochemical metabolites is anticipated to open new approaches in the coming years for managing all types of cancers. In the present chapter, we report on our efforts to determine the major strategies used to treat cancer by phytochemicals in cancer cells.