Promoting effect of Se-allylselenocysteine on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis

Se-allylselenocysteine (ASC), an analogue of garlic bioactive compound, has been shown to inhibit mammary carcinogenesis in vivo and cell growth in vitro. However, the function of ASC on anti-inflammatory effects remains largely unknown. Therefore, we investigated whether ASC has an anti-inflammatory effect on lipopolysaccharide (LPS)-induced inflammation or an anti-tumor effect promoting on DMBA/TPA-induced skin tumorigenesis and tried to elucidate the mechanisms involved. Herein, the results showed that ASC inhibited LPS-induced production of nitric oxide (NO) with a decreased protein level of inducible nitric oxide synthase (iNOS) in RAW 264.7 cells. However, ASC enhanced LPS-induced cyclooxygenase-2 (COX-2) protein levels and mRNA expression. Interestingly, we found for the first time that topical application of ASC on the dorsal skin of DMBA-initiated and TPA-promoted mice significantly accelerated skin tumorigenesis and raised tumor multiplicity as compared to the positive control group (DMBA/TPA). The number of tumours that were 1–3, 3–5, and >5 mm in size per mouse increased in a dose-dependent manner in the ASC pre-treated groups. Pre-treatment with ASC showed a significant increase in the expression of COX-2 compared with the positive control group. Thus, ASC may modulate the COX-2 protein expression and promote DMBA/TPA-induced skin cancer in mice.

[1]  M. Tsai,et al.  Se-Allylselenocysteine induces autophagy by modulating the AMPK/mTOR signaling pathway and epigenetic regulation of PCDH17 in human colorectal adenocarcinoma cells. , 2015, Molecular nutrition & food research.

[2]  Chi-Tang Ho,et al.  Chemopreventive Effects of Natural Dietary Compounds on Cancer Development , 2009 .

[3]  I. Arnault,et al.  Seleno-compounds in garlic and onion. , 2006, Journal of chromatography. A.

[4]  E. Dennis,et al.  Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically Induced Skin Cancer , 2014, Molecular Cancer Research.

[5]  A. Moreira,et al.  Potential anti-inflammatory effect of LQFM-021 in carrageenan-induced inflammation: The role of nitric oxide. , 2017, Nitric oxide : biology and chemistry.

[6]  G. F. Passos,et al.  The role of PKC/ERK1/2 signaling in the anti-inflammatory effect of tetracyclic triterpene euphol on TPA-induced skin inflammation in mice. , 2013, European journal of pharmacology.

[7]  H. Ganther,et al.  Molecular mechanisms associated with Se-allylselenocysteine regulation of cell proliferation and apoptosis. , 2001, Cancer letters.

[8]  L. Ghibelli,et al.  The Role of Cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies , 2010, International journal of cell biology.

[9]  Allan Balmain,et al.  Activation of the mouse cellular Harvey-ras gene in chemically induced benign skin papillomas , 1984, Nature.

[10]  Kaiyu Qian,et al.  Capsaicin Suppresses Cell Proliferation, Induces Cell Cycle Arrest and ROS Production in Bladder Cancer Cells through FOXO3a-Mediated Pathways , 2016, Molecules.

[11]  N. Arora,et al.  Modulatory effects of Azadirachta indica leaf extract on cutaneous and hepatic biochemical status during promotion phase of DMBA/TPA-induced skin tumorigenesis in mice. , 2013, Indian journal of biochemistry & biophysics.

[12]  H. Ganther,et al.  Chemoprevention of mammary cancer with Se-allylselenocysteine and other selenoamino acids in the rat. , 1999, Anticancer research.

[13]  K. Gungorduk,et al.  Effect of intraabdominal administration of Allium sativum (garlic) oil on postoperative peritoneal adhesion. , 2014, European journal of obstetrics, gynecology, and reproductive biology.

[14]  H. Ganther,et al.  Activity of Se‐allylselenocysteine in the presence of methionine γ‐lyase on cell growth, DNA integrity, apoptosis, and cell‐cycle regulatory molecules , 2000, Molecular carcinogenesis.

[15]  C. Nathan,et al.  Role of transcription factor NF-kappa B/Rel in induction of nitric oxide synthase. , 1994, The Journal of biological chemistry.

[16]  Chen Chen,et al.  Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice. , 2015, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[17]  Yiwei Li,et al.  Back to the future: COX-2 inhibitors for chemoprevention and cancer therapy. , 2007, Mini reviews in medicinal chemistry.

[18]  D. Nie,et al.  Cyclooxygenases, prostanoids, and tumor progression , 2007, Cancer and Metastasis Reviews.

[19]  S. Ejaz,et al.  Effect of aged garlic extract on wound healing: A new frontier in wound management , 2009, Drug and chemical toxicology.

[20]  Y. Song,et al.  Celecoxib inhibits phorbol ester-induced expression of COX-2 and activation of AP-1 and p38 MAP kinase in mouse skin. , 2003, Carcinogenesis.

[21]  Jianxiong Jiang,et al.  Cyclooxygenase-2 in glioblastoma multiforme. , 2017, Drug discovery today.

[22]  C. Kemp.  Multistep skin cancer in mice as a model to study the evolution of cancer cells. , 2005, Seminars in cancer biology.

[23]  Haw‐Wen Chen,et al.  DATS reduces LPS-induced iNOS expression, NO production, oxidative stress, and NF-kappaB activation in RAW 264.7 macrophages. , 2006, Journal of agricultural and food chemistry.

[24]  P. Dasgupta,et al.  Treating the Human Bladder with Capsaicin: Is It Safe? , 1998, European Urology.

[25]  P. Alexander.  Prostaglandins and cancer , 1982, Nature.

[26]  J. Potter,et al.  Vegetables, fruit, and cancer prevention: a review. , 1996, Journal of the American Dietetic Association.

[27]  Hye-Jin Park,et al.  Aged red garlic extract suppresses nitric oxide production in lipopolysaccharide-treated RAW 264.7 macrophages through inhibition of NF-κB. , 2015, Journal of medicinal food.

[28]  S. Prescott,et al.  Many actions of cyclooxygenase‐2 in cellular dynamics and in cancer , 2002, Journal of cellular physiology.

[29]  Hongyan Wu,et al.  Chemomodulatory efficacy of lycopene on antioxidant enzymes and carcinogen-induced cutaneum carcinoma in mice. , 2014, Food & function.

[30]  Yi-Hui Lee,et al.  Capsaicin Inhibits Multiple Bladder Cancer Cell Phenotypes by Inhibiting Tumor-Associated NADH Oxidase (tNOX) and Sirtuin1 (SIRT1) , 2016, Molecules.

[31]  N. Rice,et al.  In vivo control of NF‐kappa B activation by I kappa B alpha. , 1993, The EMBO journal.

[32]  Ki-Young Kim,et al.  Sakuranetin Inhibits Inflammatory Enzyme, Cytokine, and Costimulatory Molecule Expression in Macrophages through Modulation of JNK, p38, and STAT1 , 2016, Evidence-based complementary and alternative medicine : eCAM.

[33]  M. Narita,et al.  κ Opioid receptor ligands regulate angiogenesis in development and in tumours , 2015, British journal of pharmacology.

[34]  A. Ullrich,et al.  A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. , 2002, Cancer research.

[35]  J. DiGiovanni,et al.  Multistage carcinogenesis in mouse skin. , 1992, Pharmacology & therapeutics.

[36]  Min‐Jung Kang,et al.  Short-term heating reduces the anti-inflammatory effects of fresh raw garlic extracts on the LPS-induced production of NO and pro-inflammatory cytokines by downregulating allicin activity in RAW 264.7 macrophages. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[37]  G. T. Bowden,et al.  Detection of mutant Ha-ras genes in chemically initiated mouse skin epidermis before the development of benign tumors. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Sur Sharma,et al.  Mechanisms and clinical uses of capsaicin. , 2013, European journal of pharmacology.

[39]  Chun-di He,et al.  Baicalein Inhibits DMBA/TPA-Induced Skin Tumorigenesis in Mice by Modulating Proliferation, Apoptosis, and Inflammation , 2013, Inflammation.

[40]  K. Seibert,et al.  Role of inducible cyclooxygenase (COX-2) in inflammation. , 1994, Receptor.

[41]  J. Pouysségur,et al.  p44 mitogen-activated protein kinase (extracellular signal-regulated kinase 1)-dependent signaling contributes to epithelial skin carcinogenesis. , 2006, Cancer research.

[42]  Á. Molnár,et al.  Plant selenium toxicity: Proteome in the crosshairs. , 2019, Journal of plant physiology.

[43]  N. Vermeulen,et al.  Induction of glutathione-S-transferase mRNA levels by chemopreventive selenocysteine Se-conjugates. , 2002, Biochemical pharmacology.

[44]  F. Marks,et al.  Transgenic cyclooxygenase-2 overexpression sensitizes mouse skin for carcinogenesis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Yung-Hyun Choi,et al.  Diallyl trisulfide exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophages by suppressing the Toll-like receptor 4/nuclear factor-κB pathway. , 2015, International journal of molecular medicine.

[46]  H. Ganther,et al.  In vitro effects of Se-allylselenocysteine and Se-propylselenocysteine on cell growth, DNA integrity, and apoptosis. , 2000, Biochemical pharmacology.