Protective Effects of Silymarin Against Photocarcinogenesis in a Mouse Skin Model

Katiyar, Säntosh K.; Korman, Neil J.; Mukhtar, Hasan; Agarwal, Rajesh

doi:10.1093/jnci/89.8.556

Cited by 324 publications

(286 citation statements)

References 40 publications

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“…The topical application of TPA to mouse skin or its treatment in certain epidermal cells is known to result in a number of biochemical alterations, changes in cellular functions and histologic changes leading to skin tumor promotion. 21,22,46 Our data clearly demonstrate that topical application of PFE prior to TPA application affords significant inhibition of TPA-induced skin edema and hyperplasia ( Figs. 1 and 2).…”

Section: Discussionsupporting

confidence: 57%

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Afaq

Saleem

Krueger

et al. 2004

Intl Journal of Cancer

418

305

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Chemoprevention has come of age as an effective cancer control modality; however, the search for novel agent(s) for the armamentarium of cancer chemoprevention continues. We argue that agents capable of intervening at more than one critical pathway in the carcinogenesis process will have greater advantage over other single-target agents. Pomegranate fruit extract (PFE) derived from the tree Punica granatum possesses strong antioxidant and antiinflammatory properties. Pomegranate fruit was extracted with acetone and analyzed based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and found to contain anthocyanins, ellagitannins and hydrolyzable tannins. We evaluated whether PFE possesses antitumor-promoting effects. We first determined the effect of topical application of PFE to CD-1 mice against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced conventional markers and other novel markers of skin tumor promotion. We found that topical application of PFE (2 mg/mouse) 30 min prior to TPA (3.2 nmole/mouse) application on mouse skin afforded significant inhibition, in a time-dependent manner, against TPA-mediated increase in skin edema and hyperplasia, epidermal ornithine decarboxylase (ODC) activity and protein expression of ODC and cyclooxygenase-2. We also found that topical application of PFE resulted in inhibition of TPA-induced phosphorylation of ERK1/2, p38 and JNK1/2, as well as activation of NF-B and IKK␣ and phosphorylation and degradation of I B␣. We next assessed the effect of skin application of PFE on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated CD-1 mouse. The animals pretreated with PFE showed substantially reduced tumor incidence and lower tumor body burden when assessed as total number of tumors per group, percent of mice with tumors and number of tumors per animal as compared to animals that did not receive PFE. In TPA-treated group, 100% of the mice developed tumors at 16 weeks on test, whereas at this time in PFE-treated group, only 30% mice exhibited tumors. Skin application of PFE prior to TPA application also resulted in a significant delay in latency period from 9 to 14 weeks and afforded protection when tumor data were considered in terms of tumor incidence and tumor multiplicity. The results of our study provide clear evidence that PFE possesses antiskintumor-promoting effects in CD-1 mouse. Because PFE is capable of inhibiting conventional as well as novel biomarkers of TPAinduced tumor promotion, it may possess chemopreventive activity in a wide range of tumor models. Thus, an in-depth study to define active agent(s) in PFE capable of affording antitumorpromoting effect is warranted.

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Section: Discussionsupporting

confidence: 57%

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Afaq

Saleem

Krueger

et al. 2004

Intl Journal of Cancer

418

305

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“…Apigenin was found to be effective in the prevention of UVA/UVBinduced skin carcinogenesis in SKH-1 mice [64]. Artemisia (Artemisia inculta) and Cuminum cyminum or cumin also contain apigenin and luteolin and their derivatives in addition to plants like carrot (Daucus carota), agrimony (Agrimonia eupatoria), arnica (Arnica montana), purple coneflower (Echinacea purpurea), and eyebright (Euphrasia officinalis)-all of which have demonstrated anti-inflammatory activity when used under the right conditions [66].…”

Section: Phytochemicals Skin Cancer and Rosmentioning

confidence: 99%

Oxidative Stress and Skin Cancer: An Overview

Narendhirakannan

Hannah

2012

Ind J Clin Biochem

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Skin is the largest body organ that serves as an important environmental interface providing a protective envelope that is crucial for homeostasis. On the other hand, it is a major target for toxic insult by a broad spectrum of physical and chemical agents that are capable of altering its structure and function. There are a large number of dietary contaminants and drugs can manifest their toxicity in skin. These environmental toxicants or their metabolites are inherent oxidants and/or directly or indirectly drive the production of a variety of reactive oxidants also known as reactive oxygen species. These are short-lived entities that are continuously generated at low levels during the course of normal aerobic metabolism. These are believed to activate proliferative and cell survival signaling that can alter apoptotic pathways that may be involved in the pathogenesis of a number of skin disorders. The skin possesses an array of antioxidant defense mechanisms that interact with toxicants to obviate their deleterious effect. The ''antioxidant power'' of a food is an expression of its capability both to defend the human organism from the action of the free radicals and to prevent degenerative disorders. Plants like olive trees have their own built-in protection against the oxidative damage of the sun, and these built-in protectors function as cell protectors in our own body. Although many antioxidants have shown substantive efficacy in cell culture systems and in animal models of oxidant injury, unequivocal confirmation of their beneficial effects in human populations has proven elusive.

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“…Solar UV radiation, particularly UVB (290-320 nm), possesses suppressive effects on the immune system, 16 and can act as a tumor initiator, 17 tumor promoter 18 and co-carcinogen. 19, 20 Skin exposure to UVB radiation induces a variety of biological effects including inflammation, sunburn cell formation, immunologic alterations and induction of oxidative stress which play an important role in the generation and maintenance of UV-induced neoplasms.…”

Section: Characteristics Of Uv Radiationmentioning

confidence: 99%

Chemoprevention of photocarcinogenesis by selected dietary botanicals

Baliga

Katiyar

2006

Photochem Photobiol Sci

185

131

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Protective Effects of Silymarin Against Photocarcinogenesis in a Mouse Skin Model

Abstract: Silymarin can provide substantial protection against different stages of UVB-induced carcinogenesis, possibly via its strong antioxidant properties. Clinical testing of its usefulness is warranted.

Cited by 324 publications

References 40 publications

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

Oxidative Stress and Skin Cancer: An Overview

Chemoprevention of photocarcinogenesis by selected dietary botanicals

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