Cancer is a leading cause of death worldwide and is responsible for one in six mortalities. Furthermore, around 70% of cancer deaths in the last decade occurred in developing countries. Cancer treatments are extremely expensive and the effectiveness of chemotherapeutic drugs is limited. Consequently, treatment becomes unaffordable due to high cost, the ability to tolerate, and side-effects of these drugs resulting in increased suffering and mortality. However, around 30% of all cancer deaths could be prevented by a change in lifestyle and diet. It is well known that phytochemicals, derived from plants consumed as part of our diet, are powerful bioactive compounds and have an important role in cancer chemoprevention. In this special issue on "Phytochemicals and Cancer Chemoprevention" we will assemble articles on potential anticancer phytochemicals and agents, their molecular targets, and mechanisms of actions. Understanding the mechanism(s) of plant-derived agents against cancer will lead to a new dimension of drug invention and targets for successful intervention.
1. Herman Yeger Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Canada.
2. Md Afjalus Siraj Department of Pharmaceutical Science, Daniel K. Inouye College of Pharmacy (DKICP), University of Hawaii at Hilo, Hilo, USA.
3. Fumio Shimamoto Faculty of Health Sciences, Hiroshima Shudo University, Hiroshima, Japan.
4. Grzegorz Grynkiewicz Pharmaceutical Institute, Warsaw, Masovian District, Poland.
5. Qasim Alhadidi Department of Medicinal and Biological Chemistry, Frederic and Mary Wolfe Center 292A, University of Toledo, Toledo, USA.
6. Robert Smith Park University, Parkville, USA.
7. Zally Torres Department of Chemistry, University of Puerto Rico, Río Piedras Campus, San Juan, Puerto Rico.
8. Ajay Bommareddy Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, USA.
9. Farrukh Aqil Department of Medicine and JG Brown Cancer Center, University of Louisville, Louisville, USA.
10. John M. Pezzuto College of Pharmacy, University of Hawaii at Hilo, Hilo, USA.
11. Richard L Eckert Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, USA.
12. Maryam Foroozesh Department of Chemistry, Xavier University of Louisiana, New Orleans, USA.
13. Gary L Firestone Department of Molecular and Cell Biology and The Cancer Research Laboratory, University of California at Berkeley, Berkeley, USA.
14. Nagi B. Kumar H. Lee Moffitt Cancer Center & Research Institute, Inc., Cancer Epidemiology, MRC/CANCONT, Tampa, USA.
15. Mei Zhang Department of Biomedical Engineering, Case Western Reserve University, Cleveland, USA.
16. Randolph Arroo Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester, UK.
17. Agustín Rascón-Chu Biotechnology, Research Center for Food and Development (CIAD), Hermosillo, Mexico.
18. Nabiha Yusuf Department of Dermatology, University of Alabama at Birmingham, Birmingham, USA.
19. Farrukh Afaq Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, USA.
The list is arranged in no particular order and being updated.
Articles of special issue are free of charge for article processing.
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Title: Attribution of isoflavones as chemopreventive phytochemicals
Authors: Grzegorz Grynkiewicz
Affiliations: Łukasiewicz Research Network, Pharmaceutical Research Institute, Warsaw, Poland.
Abstract: Isoflavones were selected as a probe sample of widespread plant phenolics, to critically discuss the value of natural products for chemoprevention, particularly in the field of cancer. This small, biogenetically and structurally distinct sub-category of secondary metabolites shares basic physicochemical characteristics with other flavonoids and polyphenols, which continuously provide new drug candidates and leads for novel therapeutics. At the same time, isoflavones as constituents of soybeans, one of the principal agricultural crops globally, are present in traditional Asian cuisine as well as in many products of the modern western food technologies. In this short review, multitargeted biological activity of isoflavones is assessed, as a causative factor in chemoprevention of chronic inflammation, metabolic syndrome and in particular, in tumor development. Apart from classical pharmacology, a point of view of systems biology was included in discussion of phytochemicals significance for healthy life styles and prospective chemoprevention of ailments perceived as civilization diseases.
Title: Autophagic response by major phytochemicals against prostate cancer development
Authors: Cole Wenner, Ryan Stewart, Abigail McCabe, Ajay Bommareddy
Affiliations: Department of Pharmaceutical Sciences, Nesbitt School of Pharmacy, Wilkes University, Wilkes-Barre, Pennsylvania, PA 18766, USA.
Abstract: Phytochemicals derived from dietary sources and natural products have gained significant attention in the scientific community due to their ability to modulate various pharmacological and biological activities. Understanding the molecular mechanisms altered by the natural products to protect against various diseases including cancer will provide therapeutic benefits for their clinical utility. Autophagy, an evolutionary conserved self-digestion process that employs lysosomal-mediated enzymatic degradation has been shown to be associated with a wide range of pathological disorders, and has attracted oncology scientists over the past two decades. Studies employing natural products have concluded the induction of autophagy that serves as a cytoprotective or cytotoxic effect through different molecular pathways. In this review, we summarize four major phytochemicals and their association with autophagy in prostate cancer chemoprevention and discuss further investigation essential in understanding their mechanisms to facilitate their clinical applications for cancer prevention and treatment.
Title: Potentially deadly phytochemicals marketed as ways to cure or prevent cancer
Authors: Robert Smith
Affiliations: Park University, 8700 NW River Park Drive, Parkville, MO 64152, USA.
Abstract: There are some phytochemicals that are marketed as ways to cure and/or prevent cancer that can become deadly when over-consumed. They include fruits in the Annonaceae family, especially graviola (Annona muricata) and the North American pawpaw (Asimina triloba). They contain a class of compounds called acetogenins. They do have anticancer properties in vitro, but they can also cause an atypical form of Parkinson’s disease that does not respond to the standard first-line treatment with L-DOPA. Unfortunately, there are also peer reviewed articles claiming that the papaya tree (Carica papaya) is the same as the North American pawpaw. The fruit of the papaya tree is quite healthy and contains no known neurotoxins. At the same time, there are many dietary supplements containing either extracts or purified phenolic compounds that activate the transcription factor nuclear erythroid-2 like factor-2 (Nrf2), which then induce the transcription of endogenous antioxidant response elements (ARE). When present at moderate concentrations in fruits and vegetables, these phenolic compounds may help prevent many types of cancer by activating the Nrf2/ARE signaling system. However, at higher concentrations they may be able to over-activate this system in patients receiving chemo- or radiation therapy for cancer. This is because cancer cells can hijack the Nrf2/ARE signaling system, enabling them to survive and proliferate. Therefore, the very same compounds that can prevent cancer may become deadly if used to treat cancer – especially in patients undergoing chemo- or radiation therapy.
Title: Potential of celastrol in cancer prevention and therapy
Authors: Raghuram Kandimalla1, Maryam Zahin1, Mohammad Saeed2, Khaled S. Allemailem3, Ahmad Almatroudiy3, Farrukh Aqil1
Affiliations: 1Department of Medicine and JG Brown Cancer Center, University of Louisville, Louisville KY 40202, USA.
2Department of Biology College of Sciences, University of Hail, KSA, USA.
3Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Qassim 51431, Saudi Arabia.
Abstract: Cancer remains one of the most important health problems and a major cause of deaths worldwide. Identification and improvement of bioactive compounds that have the potential to prevent or inhibit carcinogenesis have attracted considerable interest in the past decades. Historically, plant-derived agents, such as vincristine, paclitaxel (Taxol®), docetaxel, topotecan, and irinotecan, are among the most effective cancer chemotherapeutics currently available. Nevertheless, most of these suffer from significant toxic side effects. Celastrol (CEL), a tri-terpenoid, isolated from Tripterygium wilfordii commonly known as ‘Thunder God Vine’ is an emerging compound with potent therapeutic activity against a variety of diseases. To date, the therapeutic usefulness of CEL has been explored in diverse clinical areas such as Alzheimer’s disease, systemic lupus erythematosus, arthritis rheumatoid, asthma, hypertension and against various cancer. One major advantage of CEL compared to standard chemotherapeutic agents is its ability to target multiple molecular pathways involved in initiation and progression of various cancers. Besides being a potent inhibitor of NF-κB and proteosomal activation, CEL dose-dependently inhibits KRAS protein levels, which is a known TAK1 inhibitor and has been shown to suppress basal TGF-β1 and TNF-α induced NF-κB activity. In this article, we highlight the cancer prevention, therapeutic effects of CEL, and its molecular targets that contribute to the observed anticancer activity against various cancers.