The Enzymes

• Verlag: Academic Press
• Jahr: 2015
• ISBN:
  9780128038772
• Thema: Ciencias biológicas
• Thema: Bioquímica

Volume 37 will provide details on the major chemical constituents of medicinal plants and their mechanism of action as the anticancer compounds. This special issue, in addition to the previous volume (volume 36 of the Enzyme series was on the topic of Natural Products and Cancer Signaling Targets: Isoprenoids, Polyphenols and Flavonoids), will highlight the significant advance made in the field in elucidating mechanisms of anticancer effect of the major phytochemicals.

• Contributions from leading authorities
• Informs and updates on all the latest developments in the field

Chapter One

How Phytochemicals Prevent Chemical Carcinogens and/or Suppress Tumor Growth?

S. Zahra Bathaie*^,†,1; Nasim Faridi*; Ahmad Nasimian*; Hamid Heidarzadeh*; Fuyuhiko Tamanoi^{† *} Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
^† Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA
¹ Corresponding author: email address: [email protected], [email protected]

Abstract

Phytochemicals are a powerful group of chemicals that are derived from natural resource, especially with plants origin. They have shown to exhibit chemoprevention and chemotherapeutic effects not only in cell lines and in animal models of cancer but also some of them are in the clinical trial phase I and II. Despite numerous reports of these phytochemical effects on cancer, an overview of the mechanisms of their action and their effects on various cellular and molecular functions important in the inhibition of cancer progression has been lacking. In this review, we attempt to catalogue various studies to examine the effect of phytochemicals in cancer initiation, promotion, signaling, and epigenetic changes. Because of the numerous studies in these topics, we only pointed out to some examples in each section.

Keywords

Chemoprevention

Chemotherapeutic

Mechanism of action

Epigenetic

Enzyme inhibition

Signaling pathway

1 Introduction

Cancer is a growing health problem around the world; particularly with the steady increase in life expectancy, rising levels of urbanization and industrialization, increasing the fast food consumption, and the subsequent changes in environmental conditions, including the lifestyle and production of various pollutions.

On World Cancer Day 2014, a new global cancer report was compiled by UN Agency, the International Agency for Research on Cancer (IARC), showing that as a single entity, cancer is the biggest cause of mortality worldwide with an estimated 8.2 million deaths from cancer in 2012. Thus, this report suggests that cancer is now the world's biggest killer—with the number of cases set to explode in coming years. In fact, World Health Organization (WHO) indicates a 70% increase over next 20 years in worldwide cancer cases. Low- and middle-income countries are most at risk of cancer overwhelming their health systems and hindering economic growth, as they have the least resources and infrastructure to cope with the predicted levels of disease escalation. Restrictions on alcohol and sugar need to be considered, say WHO scientists as there now exists a “real need” to focus on cancer prevention by tackling smoking, obesity, and drinking. Compiled by IARC, The World Cancer Report series is recognized as an authoritative source of global perspective and information on cancer. The first volume appeared in 2003 and the second in 2008. The third volume in the series was released in 2014.

The concept of a “magic bullet” was popularized by “Paul Ehrlich” (March 14, 1854–August 20, 1915) a German physician and scientist, who worked in the fields of hematology, immunology, and chemotherapy. He defined a “magic bullet” as an ideal therapeutic agent that would be created and killed only the organism targeting a disease. He reasoned that if a compound could be made that selectively targeted a disease-causing organism, then it could be selectively delivered to that organism; this compound or “magic bullet” could only kill the target organism. This concept is now known as “targeted therapy” [1].

Since there appears to be no “magic bullet” to treat a diverse type of cancer, it has been apparent that cancer risks can be reduced by eliminating or at least minimizing the exposure to known carcinogens [2]. In 1981, Doll and Peto in a report based on the statistical and epidemiological data have announced that among all risk factors of cancer—tobacco, alcohol, occupation, and so on—about 35% (10–70%) of human cancer mortality is attributed to diet [3]. Although, it is a wide range variant, but it indicates the importance of diet as a risk factor of cancer. On the other hand, an inverse relationship between the risk of specific cancers and consumption of vegetables and fruits have been reported [2]. These indicate the importance of Phyto products in diet and in the life.

Phytochemicals (“Phyto” is from the Greek word meaning plant) are nonnutritive components in the plant-based diet that possess substantial anticarcinogenic and antimutagenic properties [2]. Phytochemicals have different roles in both cancer prevention and treatment. Despite remarkable progress in understanding the carcinogenic process and devising preventive/therapeutic effects of phytochemicals, the mechanisms of action of most phytochemicals have not yet been fully understood. Bioavailability, toxicity, pharmacodynamic, and pharmacokinetics of the plant components(s) should be investigated. Oral consumption of some phytochemicals results in lower plasma/serum concentration. The reasons for this include: low intestinal absorption, degradation by intestinal enzymes, and/or metabolization by phase I and/or II detoxifying enzymes. For example, crocin intestinal absorption is low and most of the orally consumed crocin appeared in the feces of rats [4]. In addition, it is degraded by the intestinal enzymes and after 2 h of oral administration of crocin, crocetin was detected in the serum of human subject [5]. Thus, oral administration of crocin may have low efficacy for therapeutic purposes, and it should be better that it is administered via injection [6].

In addition, adverse (or side) effects of phytochemicals should be considered. For example, there are several hundred published research articles and many review papers about the beneficial effects of resveratrol in various diseases, in both in vivo and in vitro studies [7–11]. Resveratrol is the most important stilbene related to cancer, and it is present in the foods like peanuts, pistachios, grapes, red and white wine, blueberries, cranberries, and even cocoa and dark chocolate. It possesses a natural antiproliferative activity, due to its role as a phytoalexin (plant antibiotic). It also increased the antitumor activity of several other drugs, such as rapamycin in breast cancer and gemcitabine in pancreatic cancer, both in vitro and in vivo [12]. Resveratrol affects all three stages of carcinogenesis, including: tumor initiation, promotion, and progression. It was found that it acts as an antioxidant and antimutagen, and induces phase II drug-metabolizing enzymes (anti-initiation activity). It also mediated anti-inflammatory effects and inhibited COX¹ and hydroperoxidase functions, as well as both COX-2 and MM-9² expression. It is a potent inhibitor of nuclear factor NF-κB activation in DMBA³-induced breast cancer in female Sprague-Dawley rats and other tumor types. Treatment of human breast cancer MCF-7 cells with resveratrol, in addition to the suppression of NF-κB activation, inhibited proliferation at S/G2/M phase (antipromotion activity). Extensive in vitro studies also revealed multiple intracellular targets of resveratrol, which in addition to inflammation, cell growth, and proliferation affect other targets like apoptosis, angiogenesis, invasion, and metastasis. Resveratrol induces human promyelocytic leukemia cell differentiation (antiprogression activity). It inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. Several other known targets of resveratrol are including: tumor suppressor p53 and Rb⁴; cell cycle regulators, cyclins, CDKs, p21WAF1, p27KIP and INK, and the checkpoint kinases ATM/ATR; transcription factors NF-κB, AP-1, c-Jun, and c-Fos; angiogenic and metastatic factors, VEGF, and matrix metalloprotease 2/9; and apoptosis and survival regulators, Bax, B...

Inhaltsverzeichnis

• Cover image
• Title page
• Table of Contents
• Copyright
• Contributors
• Preface
• Chapter One: How Phytochemicals Prevent Chemical Carcinogens and/or Suppress Tumor Growth?
• Chapter Two: Quercetin and Tryptanthrin: Two Broad Spectrum Anticancer Agents for Future Chemotherapeutic Interventions
• Chapter Three: Potential Anticancer Properties and Mechanisms of Action of Withanolides
• Chapter Four: Prenylated Dihydrochalcones from Artocarpus altilis as Antiausterity Agents
• Chapter Five: Mechanisms of the Anticancer Effects of Isothiocyanates
• Chapter Six: Mechanism of the Anticancer Effect of Lycopene (Tetraterpenoids)
• Chapter Seven: Anticancer Mechanism of Sulfur-Containing Compounds
• Chapter Eight: The Role of Soy Phytoestrogens on Genetic and Epigenetic Mechanisms of Prostate Cancer
• Author Index
• Subject Index