New Enlightenment of Skin Cancer Chemoprevention through Phytochemicals: In Vitro and In Vivo Studies and the Underlying Mechanisms (original) (raw)
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Chemoprevention of Skin Cancer with Dietary Phytochemicals
Skin Cancer Overview, 2011
2. Ultraviolet (UV) radiation-induced skin cancer and chemoprevention with dietary phytochemicals Currently, skin cancer occurs at a rate of one in every six Americans (18%), and constitutes more than 30% of all newly diagnosed cancer patients in the world (Gloster et al., 1996; Aziz et al., 2005). The incidence and mortality in the skin cancer have rapidly increased worldwide because of an increase in the level of UV radiation at the earth's surface due to ozone depletion. The new strategies for skin cancer prevention and treatment are demanded, and chemoprevention has come to the fore. www.intechopen.com Skin Cancer Overview 174 2.1 Skin cancer Epidemiological researches on the relation between diseases and death have demonstrated a significant death rate decrease in stroke, heart and infectious diseases within the United States, however, cancer mortality rate has not been changed in last 50 years (Aggarwal & Shishodia, 2006). In spite of a better understanding of the cancer mechanism and improvement of medical and pharmacological technology, the efficiency of cancer treatment has not progressed. In various types of cancer, especially, skin cancer has recognized a serious public health issue because of rapid increase of incidence, morbidity and mortality (Katiyar, 2011). There are over one million patients per year diagnosed skin cancer in the United States, and these account for 40% of all new cases of cancer diagnosed (Gloster et al., 1996; Johnson et al., 1998). Magnitude of the skin cancer is closely associated with exposure to UV radiation. Indeed, the high incidence of skin cancer is reported in some countries of the world such as Australia (particularly in Queensland) indicating serious destruction of ozone layer (Diepgen & Mahler, 2002). Depending on the cellular origin, skin cancer is divided into two major categoriesmelanomas (melanocytic) and non-melanoma (epithelial) skin cancers (NMSCs), and NMSCs are subdivided into basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). Although both BCCs (the most common types of skin cancer, 80%) and SCCs are derived from the basal layer of the epidermis of the skin, BCCs and SCCs have a different feature-BCCs are characterized by slow growth and rare metastasis, whereas, SCCs have strong invasive and metastasis ability. Melanomas account for only 4% of skin cancer, but it is the main cause of death in patients with skin cancer (Marks, 1995). 2.1.1 UV radiation as a major risk factor for skin damages Although various physical, chemical and environmental factors contribute to initiation and development of skin disorders-premature skin aging, wrinkling, scaling, dryness, mottled pigment abnormalities and skin cancer, UV radiation exerts the most detrimental effect in skin (Nichol & Katiyar, 2010; Katiyar, 2011). Among invisible radiation emitted from the sun, UV radiation is classified into three categories according to its wavelength: UV-A (315-380 nm), UV-B (280-315 nm), and UV-C (190-280 nm) (Tyrrell, 1994). Because stratospheric ozone layer completely absorbs UV-C and mostly absorbs UV-B radiation, it has been considered that UV radiation reaching the surface of the earth is composed with 10% of the UV-B and 90% of the UV-A radiation. However, recently, the proportion of UV-B radiation at the surface of the earth has gradually increased due to depletion of the ozone layer (Latonen & Laiho, 2005). Although UV-B radiation accounts for a minor part of the sunlight arriving to the surface of the earth, previous studies have suggested that UV-B radiation could have the most cytotoxic and mutagenic effect to induce skin damage including skin cancer (Ichihashi et al., 2003). 2.2 UV-B radiation-induced cellular mechanisms in skin UV-B radiation can cross the whole epidermis layer and portion of the dermis compartment in skin. UV-B radiation can induce both direct and indirect adverse biological effects including induction of DNA damage, oxidative stress, inflammation, immunosuppression, alterations in the extracellular matrix (ECM) and premature aging of the skin (Mukhtar & Elmets, 1996; Latonen & Laiho, 2005), which together perform critical functions in the generation and maintenance of UV-induced carcinogenesis (Hruza & Pentland, 1993). Actually, it is experimentally demonstrated that UV-B radiation can act as a strong carcinogen in mouse skin www.intechopen.com
Potent Role of Antioxidant Molecules in Prevention and Management of Skin Cancer
Journal of Clinical & Experimental Dermatology Research, 2017
Evidence reported that cancers are spreading every nook and corner of the world at an alarming rate. Skin diseases like chronic skin inflammations, psoriasis and skin cancers have also been burning topic in today. Protections of a biological system are often hampered while skin gets damaged. Factors like UV, radiation, viruses, chronic diseases, genetic predispositions, food habits and environmental exposures might lead to skin cancers. In addition to these, urbanization and globalization may also contaminate the environment that may eventually modify several biological and genetic functions. USA, Europe and Australia are in the most dangerous zone to be exposed. We basically performed detailed search of PubMed, Google Scholar and Science Direct for literature search and collecting related information. On the other hand, experiments suggested that antioxidant components such as phenolic acid derivatives, flavonoids and flavonol found to be preventive against cancer cell proliferations. Moreover, antioxidants have been also evaluated as a protective agent against chronic inflammatory diseases as well. These molecules may participate as an additional therapy which could exert synergistic effects while applying with other chemotherapeutic agents. Our literature findings and hypothetical figure may establish a good correlation between skin cancer and antioxidant therapy. Therefore this study will be focused on skin cancer biology and some possible management strategies using antioxidant phyto-nutrients.
Antioxidants
Human skin is continuously subjected to environmental stresses, as well as extrinsic and intrinsic noxious agents. Although skin adopts various molecular mechanisms to maintain homeostasis, excessive and repeated stresses can overwhelm these systems, leading to serious cutaneous damage, including both melanoma and non-melanoma skin cancers. Phytochemicals present in the diet possess the desirable effects of protecting the skin from damaging free radicals as well as other benefits. Dietary phytochemicals appear to be effective in preventing skin cancer and are inexpensive, widely available, and well tolerated. Multiple in vitro and in vivo studies have demonstrated the significant anti-inflammatory, antioxidant, and anti-angiogenic characteristics of dietary phytochemicals against skin malignancy. Moreover, dietary phytochemicals affect multiple important cellular processes including cell cycle, angiogenesis, and metastasis to control skin cancer progression. Herein, we discuss the a...
Chemopreventive Mechanisms of Natural Products in Oral, Mammary and Skin Carcinogenesis: An Overview
The Open Nutraceuticals Journal
Cancer is a major cause of morbidity and mortality worldwide and represents a tremendous burden to the individual, family and society. External factors such as tobacco, chemicals, radiation, viruses and internal factors such as inherited mutations and immune status may act together or in sequence to initiate or promote carcinogenesis. Cancer chemoprevention is recognized as the most promising and novel approach to prevent, inhibit or reverse the carcinogenic processes by intervention with natural products or synthetic chemical substances. A large number of traditional medicinal plants and their active principles were reported to have chemopreventive properties. Chemopreventive agents may act on one or several steps [initiation, promotion, progression] of carcinogenesis. Agents that possess antimutagenic, anticarcinogenic, inhibitory effects on cell proliferation, antioxidant function and modulating effect on carcinogen detoxification are considered as good chemopreventive agents. The aim of the present review paper is to provide the list of chemopreventive agents and their mechanism of actions, reported for the past 10 to 15 years, against chemical carcinogen induced oral, mammary and skin carcinogenesis.
Novel Approaches to Chemoprevention of Skin Cancer
Journal of Dermatology, 2000
Protection against sun-induced damage leading to photocarcinogenesis in skin is a highly desirable goal. Among various strategies, chemopreventive approaches utilizing non-toxic agents to prevent the occurrence of precancerous lesions or their surrogate markers are potentially attractive. Epidemiological and experimental studies provide evidence that some naturally occurring chemical agents in the human diet can diminish cancer risk. Aside from water, tea is the most common beverage consumed worldwide. Black tea accounts for nearly 80% of total tea production. Black tea and green tea are derived from the same plant, Camelia sinensis. Green tea contains monomeric polyphenols known as flavanols and black tea contains dimeric flavanols and polymeric polyphenols known as theaflavins (TFs) and thearubigins (TRs). Over the past fifteen years our laboratory has been exploring the feasibility of using tea and its constituents as an approach to skin cancer prevention. We demonstrated that green tea, black tea and constituent polyphenols protect against chemical-and ultraviolet B (UVB)-induced carcinogenesis and reduce the growth of established tumors in skin. We have also shown the efficacy of green and black tea extracts against UVB and psoralen + ultraviolet A (PUVA)-induced early damage in skin. Although PUVA is highly effective in treating certain skin diseases, careful follow-up studies of cohorts of patients have shown that similar to UVB, PUVA treatment increases the risk for cutaneous squamous cell carcinoma and melanoma. We have found that oral administration of a standardized green tea extract (SGTE) prior to and during treatment of SKH-I mice diminished PUVA-induced skin hyperplasia and hyperkeratosis. SGTEtreatment also inhibited PUVA-induced accumulation of c-fos and p53 proteins and epithelial hyperproliferation. Both topical application and oral administration of SGTE after PUVA-treatment reduced skin inflammation and cell hyperproliferation. Topical application of SGTE to human skin prior to PUVA-treatment inhibited the delayed skin inflammatory response. Similarly, oral and topical administration of standardized black tea extract (SBTE) and its two major polyphenolic sub-fractions protect against UVB-induced erythema in SKH-I mice. Furthermore, topical application of tea extracts to human volunteers protects against UVB-induced erythema. In summary, these studies indicate that tea extracts are effective in reducing UVB-and PUVA-mediated DNA damage, expression of early response genes and early inflammatory changes in skin. These studies verify a conceptual rationale for employing naturally occurring dietary constituents as an approach to cancer chemoprevention.
Plant derived anticancer agents: A green approach towards skin cancers
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018
Plants have been used as medicinal agents since the origin of mankind. High cost and severe side effects associated with conventional chemotherapy has limited their general acceptability and fuel up the search for alternate options. The alternative treatment options like phytochemicals have come up with ease of availability and cost effectiveness. Owing to their general acceptance, safety, low side effects and multistep targeting in signal transduction pathways, plant derived phyto-constituents have promising anti-carcinogenic potential for skin related cancers. This leads to the surge in research of new phytochemicals for the prevention and cure of a variety of skin cancers which are major cause of morbidity and mortality in present world. Although very limited clinical data involving humans is available in literature to demonstrate favorable eff ;ects of phyto-constituents on various types of skin carcinomas yet the topical treatment with these plant derived anticancer phytochemica...
Review of Natural Compounds for Potential Skin Cancer Treatment
Molecules, 2014
Most anti-cancer drugs are derived from natural resources such as marine, microbial and botanical sources. Cutaneous malignant melanoma is the most aggressive form of skin cancer, with a high mortality rate. Various treatments for malignant melanoma are available, but due to the development of multi-drug resistance, current or emerging chemotherapies have a relatively low success rates. This emphasizes the importance of discovering new compounds that are both safe and effective against melanoma. In vitro testing of melanoma cell lines and murine melanoma models offers the opportunity for identifying mechanisms of action of plant derived compounds and extracts. Common anti-melanoma effects of natural compounds include potentiating apoptosis, inhibiting cell proliferation and inhibiting metastasis. There are different mechanisms and pathways responsible for anti-melanoma actions of medicinal compounds such as promotion of caspase activity, inhibition of angiogenesis and inhibition of the effects of tumor promoting proteins such as PI3-K, Bcl-2, STAT3 and MMPs. This review thus aims at providing an overview of anti-cancer compounds, derived from natural sources, that are currently used in cancer chemotherapies, or that have been reported to show anti-melanoma, or anti-skin cancer activities. Phytochemicals that are discussed in this review include flavonoids, carotenoids, terpenoids, vitamins, sulforaphane, some polyphenols and crude plant extracts.
Recent Advances in Phenolic Metabolites and Skin Cancer
International Journal of Molecular Sciences
Skin cancer represents any tumor development from the cutaneous structures within the epidermis, dermis or subcutaneous tissue, and is considered to be the most prevalent type of cancer. Compared to other types of cancer, skin cancer is proven to have a positive growth rate of prevalence and mortality. There are available various treatments, including chemotherapy, immunotherapy, radiotherapy and targeted therapy, but because of the multidrug resistance development, a low success has been registered. By this, the importance of studying naturally occurring compounds that are both safe and effective in the chemoprevention of skin cancer is emphasized. This review focuses on melanoma because it is the deadliest form of skin cancer, with a significantly increasing incidence in the last decades. As chemopreventive agents, we present polyphenols and their antioxidant activity, anti-inflammatory effect, their ability to balance the cell cycle and to induce apoptosis and their various other...