Anticancer Activity of Natural Products and Related Compounds

Nature has always been a precious source of bioactive molecules which are used for the treatment of various diseases [...].

Nature has always been a precious source of bioactive molecules which are used for the treatment of various diseases [1].Natural compounds such as dietary phytochemicals, nutritional herbs, and their constitutive bioactive agents possess a great variety of chemical scaffolds and distinct bioactivity profiles, which make them suitable for applications in therapy or as valuable lead compounds to obtain novel potent bioactive compounds [2].Significant advances in natural source isolation and extraction techniques have led to the identification of novel compounds as useful starting points for the generation of optimized molecules with enhanced therapeutic potential via semi-synthetic or synthetic processes [3].
The application of natural products in the field of chemotherapy and chemoprevention is a valuable research topic, leading to the extensive use of plant-derived compounds as potent antitumor molecules [4].In addition, marine-based pharmaceuticals have been extensively studied for their applications in the anticancer field, providing useful compounds such as cytarabine and trabectedin [5].Alternative treatments in complement with traditional methods (radiotherapy, chemotherapy, and surgery) have been shown to be helpful and offer very reasonable alternatives to current medicines for cancer [6].Much effort has also been directed towards the discovery of novel targets [7][8][9] in an attempt to obtain anticancer effects via multiple mechanisms, overcoming the resistance phenomena developed by most cancers.
Natural products effectively inhibit cell proliferation, regulate the cell cycle, and interfere with several tumorigenic signaling pathways [10,11].The anticancer properties of polyphenols, found abundantly in plants, as flavonoids [12], terpenoids [13], and alkaloids [14], have been extensively reported [15].However, important research efforts are necessary to fully understand the mechanisms of action of natural compounds by which these agents affect cell proliferation, differentiation, apoptosis, angiogenesis, and metastasis; in addition, there is a need to overcome major problems such as toxicity, poor selectivity, and unfavorable pharmacokinetics [16].
Currently, many plant-based antitumor drugs are in clinical use, such as taxanes, vinblastine, vincristine, and podophyllotoxin analogues.The combined use of phytochemicals like resveratrol, curcumin, and thymoquinone with other antitumor agents has shown significant success in preclinical studies, allowing enhanced efficacy and mitigation of side effects [17,18].Emerging nanotechnology applications for anticancer drug formulations have been revolutionizing cancer therapy.Tissue-specific nanomedicines play a key role in advanced cancer diagnostic techniques by using liposomes, micelles, and nanoparticles as effective delivery vehicles [19].Moreover, medicinal plant extracts have proven most effective in various cancers, paving the way for developing novel therapeutic strategies [20].Many studies have been based on crude aqueous and ethanol extracts, with few explorations of their mechanisms [21].
In this Topic, 30 original articles and 3 reviews have been collected, with a particular focus on the isolation of bioactive compounds from natural sources, the mechanisms of action of anticancer compounds at the cellular level, and the application of active molecules against a panel of solid and hematological cancers, including melanoma, breast, lung, colorectal, prostate, bladder, and gastric cancer.Most of the analyzed compounds were from natural sources, whereas some semi-synthetic derivatives were also identified and discussed.
The extracts and the isolated components have proven effective against breast, colorectal, lung, bladder, myeloma, and prostate cancer through several mechanisms, including decreased tumor cell viability, modulation of cytokines, secretion of chemokines, modulation of ROS, reduction of specific MMP subtypes, apoptosis, cell cycle inhibition, or by downregulating MAPK.
Table 1 schematically illustrates the content of this Topic, with all the contributions published in the six participating journals.

Table 1 .
Original articles and reviews collected in the six journals participating in the Topic.