Effective inhibition of skin cancer, tyrosinase, and antioxidative properties by astaxanthin and astaxanthin esters from the green alga Haematococcus pluvialis.

Astaxanthin mono- (AXME) and diesters (AXDE) were characterized and examined for anticancer potency with total carotenoids (TC) and astaxanthin (AX) against UV-7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer model in rat. At 200 μg/kg bw, AXDE and AXME reduced UV-DMBA-induced tumor incidences up to 96 and 88%, respectively, when compared to AX (66%) and TC (85%). UV-DMBA has been known to generate high levels of free radicals and tyrosinase enzyme, leading to characteristic symptoms of skin pigmentation and tumor initiation. Intriguingly, ~7-fold increase in tyrosinase and 10-fold decrease in antioxidant levels were normalized by AXDE and AXME as opposed to only ~1.4-2.2-fold by AX and TC, respectively. This result together with the appearance of 72 and 58 ng/mL of retinol in the serum of respective AXE-treated (AXDE + AXME) and AX-treated animals suggested that better anticancer potency of AXEs could be due to increased bioavailability.

[1]  S. Andrei,et al.  Effects of astaxanthin supplementation on chemically induced tumorigenesis in Wistar rats , 2012, Acta Veterinaria Scandinavica.

[2]  F. Brugè,et al.  Nitroxides and a nitroxide-based UV filter have the potential to photoprotect UVA-irradiated human skin fibroblasts against oxidative damage. , 2011, Journal of dermatological science.

[3]  S. Dharmesh,et al.  Gastroprotective Effect of Ginger Rhizome (Zingiber officinale) Extract: Role of Gallic Acid and Cinnamic Acid in H+, K+-ATPase/H. pylori Inhibition and Anti-Oxidative Mechanism , 2011, Evidence-based complementary and alternative medicine : eCAM.

[4]  A. G. Rao,et al.  Erratum to “Interaction of sesamol (3,4-methylenedioxyphenol) with tyrosinase and its effect on melanin synthesis” [Biochimie. vol. 93 (2011) p. 562–569] , 2011 .

[5]  Vismaya,et al.  Gastroprotective Properties of Karanjin from Karanja (Pongamia pinnata) Seeds; Role as Antioxidant and H+, K+-ATPase Inhibitor , 2011, Evidence-based complementary and alternative medicine : eCAM.

[6]  K. Alitalo,et al.  Suppressive Effects of Vascular Endothelial Growth Factor-B on Tumor Growth in a Mouse Model of Pancreatic Neuroendocrine Tumorigenesis , 2010, PloS one.

[7]  W. Shin,et al.  Pharmacokinetics and first-pass metabolism of astaxanthin in rats , 2010, British Journal of Nutrition.

[8]  Gokare A. Ravishankar,et al.  Characterization of microalgal carotenoids by mass spectrometry and their bioavailability and antioxidant properties elucidated in rat model. , 2010, Journal of agricultural and food chemistry.

[9]  V. Baskaran,et al.  Antioxidant and cytotoxic effect of oxidized lutein in human cervical carcinoma cells (HeLa). , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[10]  G. Imokawa,et al.  Astaxanthin attenuates the UVA-induced up-regulation of matrix-metalloproteinase-1 and skin fibroblast elastase in human dermal fibroblasts. , 2010, Journal of dermatological science.

[11]  R. Ambati.  Characterization of micro algal carotenoids by mass spectrometry and their bioavailability and antioxidant properties in rat model , 2010 .

[12]  G. Sudhandiran,et al.  Astaxanthin inhibits tumor invasion by decreasing extracellular matrix production and induces apoptosis in experimental rat colon carcinogenesis by modulating the expressions of ERK-2, NFkB and COX-2 , 2011, Investigational New Drugs.

[13]  Yoon-Sik Lee,et al.  Kojic acid-amino acid conjugates as tyrosinase inhibitors. , 2009, Bioorganic & medicinal chemistry letters.

[14]  E. Camera,et al.  Astaxanthin, canthaxanthin and β‐carotene differently affect UVA‐induced oxidative damage and expression of oxidative stress‐responsive enzymes , 2009, Experimental dermatology.

[15]  M. Soni,et al.  Safety assessment of astaxanthin-rich microalgae biomass: Acute and subchronic toxicity studies in rats. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[16]  Gokare A. Ravishankar,et al.  Ulcer preventive and antioxidative properties of astaxanthin from Haematococcus pluvialis. , 2008, European journal of pharmacology.

[17]  S. Dharmesh,et al.  A novel phenol-bound pectic polysaccharide from Decalepis hamiltonii with multi-step ulcer preventive activity. , 2007, World journal of gastroenterology.

[18]  M. Horswill,et al.  Social Cognitive Predictors of Sun Protection Intention and Behavior , 2006, Behavioral medicine.

[19]  Jeong Ah Kim,et al.  Inhibitory effect of piperlonguminine on melanin production in melanoma B16 cell line by downregulation of tyrosinase expression. , 2006, Pigment cell research.

[20]  N. Mukherjee,et al.  Inhibitory effects of Azadirachta indica on DMBA-induced skin carcinogenesis in Balb/c mice , 2006, Molecular and Cellular Biochemistry.

[21]  B. Longley,et al.  Chemoprevention of skin cancer by grape constituent resveratrol: relevance to human disease? , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  T. Dragani,et al.  Loss of tyrosinase activity confers increased skin tumor susceptibility in mice , 2004, Oncogene.

[23]  N. O'Brien,et al.  The effect of carotenoids and tocopherols in the protection of human fibroblast cells against UVA-induced DNA damage. , 2004, Journal of dermatological science.

[24]  A. Nagao,et al.  Phospholipids affect the intestinal absorption of carotenoids in mice , 2003, Lipids.

[25]  N. O'Brien,et al.  Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated cells in culture. , 2002, Journal of dermatological science.

[26]  Gokare A. Ravishankar,et al.  Influence of stress on astaxanthin production in Haematococcus pluvialis grown under different culture conditions , 2002 .

[27]  H. Mukhtar,et al.  Chemoprevention of Skin Cancer through Natural Agents , 2001, Skin Pharmacology and Physiology.

[28]  K. Kitahama,et al.  Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. , 2001, Biochimica et biophysica acta.

[29]  R T Lorenz,et al.  Commercial potential for Haematococcus microalgae as a natural source of astaxanthin. , 2000, Trends in biotechnology.

[30]  I. Yaylim,et al.  The effects of Brassica oleraceae var capitata on epidermal glutathione and lipid peroxides in DMBA-initiated-TPA-promoted mice. , 2000, Anticancer research.

[31]  J. P. Yuan,et al.  Hydrolysis kinetics of astaxanthin esters and stability of astaxanthin of Haematococcus pluvialis during saponification. , 1999, Journal of agricultural and food chemistry.

[32]  I. Kubo,et al.  Tyrosinase Inhibitors from Cumin , 1998 .

[33]  S. Lippman,et al.  Cancer chemoprevention. Part 1: Retinoids and carotenoids and other classic antioxidants. , 1998, Oncology.

[34]  N. O'Brien,et al.  Short communication Modulation of UVA light-induced oxidative stress by b-carotene, lutein and astaxanthin in cultured fibroblasts , 1998 .

[35]  A. Baum,et al.  Successful behavioral interventions to prevent cancer: the example of skin cancer. , 1998, Annual review of public health.

[36]  M. Sporn.  The war on cancer , 1996, The Lancet.

[37]  R. Agarwal,et al.  Chemoprevention of Photocarcinogenesis , 1996, Photochemistry and photobiology.

[38]  M. Maudet,et al.  Vitamin A status and metabolism of cutaneous polyamines in the hairless mouse after UV irradiation: action of beta-carotene and astaxanthin. , 1995, International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition.

[39]  M. Leary,et al.  Effects of appearance-based admonitions against sun exposure on tanning intentions in young adults. , 1994, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[40]  M. Sporn.  Chemoprevention of cancer. , 1993, Lancet.

[41]  M. Wick,et al.  Role of ultraviolet radiation in the induction of melanocytic tumors in hairless mice following 7,12-dimethylbenz(a)anthracene application and ultraviolet irradiation. , 1991, Cancer research.

[42]  H. Bergmeyer.  IFCC methods for the measurement of catalytic concentrations of enzymes: Part 3. IFCC method for alanine aminotransferase (L-alanine: 2-oxoglutarate aminotransferase, EC 2.6.1.2)☆ , 1980 .

[43]  F. Ceriotti,et al.  INTERNATIONAL FEDERATION OF CLINICAL CHEMISTRY AND LABORATORY MEDICINE (IFCC). METHODS FOR THE MEASUREMENT OF CATALYTIC CONCENTRATIONS OF ENZYMES. PART 3. IFCC METHOD FOR ALANINE AMINOTRANSFERASE , 1980 .

[44]  S. Aust,et al.  Microsomal lipid peroxidation. , 1978, Methods in enzymology.

[45]  M. Hørder,et al.  Provisional recommendations on IFCC methods for the measurement of catalytic concentrations of enzymes. Part 2. IFCC method for aspartate aminotransferase. , 1977, Clinica chimica acta; international journal of clinical chemistry.

[46]  G. Szász.  New substrates for measuring gamma-glutamyl transpeptidase activity. , 1974, Zeitschrift fur klinische Chemie und klinische Biochemie.

[47]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.