Astaxanthin and Cancer: A Comprehensive Review of Research

Sana  Ebran Safahi; Narges Nikoonahad Lotfabadi

doi:10.63053/ijhes.82

Authors

Sana Ebran Safahi Biology Department, Faculty of Sciences, Science and Arts University, Yazd, Iran
Narges Nikoonahad Lotfabadi PhD in Developmental Biology, Assistant Professor, Department of Biology, Faculty of Sciences, Science and Arts University, Yazd, Iran. https://orcid.org/0000-0003-2214-7268

DOI:

https://doi.org/10.63053/ijhes.82

Keywords:

Astaxanthin; Cancer; Anticancer Properties; Antioxidant Propeties; Cancer Prevention

Abstract

Astaxanthin, a red carotenoid pigment abundantly present in seafood and microalgae, has garnered increasing attention for its potential therapeutic implications in cancer. This article delves into the scientific intricacies surrounding astaxanthin and its direct effects on cancer cells. Astaxanthin exhibits remarkable anti-cancer properties, including the inhibition of cancer cell proliferation, induction of apoptosis, and suppression of metastatic processes. At the molecular level, astaxanthin showcases anti-proliferative effects through modulation of cell cycle regulators, disrupting the uncontrolled growth of cancer cells. Additionally, its ability to induce apoptosis, a programmed cell death mechanism, presents a promising avenue for curtailing aberrant cell survival. Furthermore, astaxanthin exhibits a notable impact on metastasis, inhibiting the migration and invasion of cancer cells through interference with key signalling pathways involved in these processes. This article also outlines the natural sources of astaxanthin, predominantly derived from microalgae and seafood, emphasizing its bioavailability and potential for integration into cancer therapeutic strategies. The scientific insights presented here aim to contribute to the growing body of knowledge surrounding astaxanthin and its application as a natural compound with significant anti-cancer potential. As research progresses, astaxanthin holds promise as a candidate for novel therapeutic interventions in the ongoing battle against cancer.

Author Biography

Narges Nikoonahad Lotfabadi, PhD in Developmental Biology, Assistant Professor, Department of Biology, Faculty of Sciences, Science and Arts University, Yazd, Iran.

*Corresponding author

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin [Internet]. 2021;71(3):209–49. Available from: https://acsjournals.onlinelibrary.wiley.com/doi/abs/10.3322/caac.21660

Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther [Internet]. 2021;6(1):201. Available from: https://doi.org/10.1038/s41392-021-00572-w

Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, et al. New approaches and procedures for cancer treatment: Current perspectives. SAGE open Med. 2021;9:20503121211034370.

Falzone L, Salomone S, Libra M. Evolution of Cancer Pharmacological Treatments at the Turn of the Third Millennium. Front Pharmacol. 2018;9:1300.

Garcia-Oliveira P, Otero P, Pereira AG, Chamorro F, Carpena M, Echave J, et al. Status and Challenges of Plant-Anticancer Compounds in Cancer Treatment. Vol. 14, Pharmaceuticals. 2021.

Elbahnaswy S, Elshopakey GE. Recent progress in practical applications of a potential carotenoid astaxanthin in aquaculture industry: a review. Fish Physiol Biochem [Internet]. 2023; Available from: https://doi.org/10.1007/s10695-022-01167-0

Sun J, Yan J, Dong H, Gao K, Yu K, He C, et al. Astaxanthin with different configurations: sources, activity, post modification, and application in foods. Curr Opin Food Sci [Internet]. 2023;49:100955. Available from: https://www.sciencedirect.com/science/article/pii/S2214799322001576

Bjørklund G, Gasmi A, Lenchyk L, Shanaida M, Zafar S, Mujawdiya PK, et al. The Role of Astaxanthin as a Nutraceutical in Health and Age-Related Conditions. Molecules. 2022 Oct;27(21).

Jelic MD, Mandic AD, Maricic SM, Srdjenovic BU. Oxidative stress and its role in cancer. J Cancer Res Ther. 2021;17(1):22–8.

Fishbein A, Hammock BD, Serhan CN, Panigrahy D. Carcinogenesis: Failure of resolution of inflammation? Pharmacol Ther. 2021 Feb;218:107670.

Ni X, Yu H, Wang S, Zhang C, Shen S. Astaxanthin Inhibits PC-3 Xenograft Prostate Tumor Growth in Nude Mice. Mar Drugs. 2017 Mar;15(3).

McCall B, McPartland CK, Moore R, Frank-Kamenetskii A, Booth BW. Effects of Astaxanthin on the Proliferation and Migration of Breast Cancer Cells In Vitro. Antioxidants (Basel, Switzerland). 2018 Oct;7(10).

Donoso A, González-Durán J, Muñoz AA, González PA, Agurto-Muñoz C. “Therapeutic uses of natural astaxanthin: An evidence-based review focused on human clinical trials.” Pharmacol Res [Internet]. 2021;166:105479. Available from: https://www.sciencedirect.com/science/article/pii/S1043661821000633

Chen Y-T, Kao C-J, Huang H-Y, Huang S-Y, Chen C-Y, Lin Y-S, et al. Astaxanthin reduces MMP expressions, suppresses cancer cell migrations, and triggers apoptotic caspases of in vitro and in vivo models in melanoma. J Funct Foods [Internet]. 2017;31:20–31. Available from: https://www.sciencedirect.com/science/article/pii/S1756464617300051

Pertiwi H, Nur Mahendra MY, Kamaludeen J. Astaxanthin as a Potential Antioxidant to Improve Health and Production Performance of Broiler Chicken. Vet Med Int. 2022;2022:4919442.

Lim KC, Yusoff FM, Shariff M, Kamarudin MS. Astaxanthin as a feed supplement in aquatic animals. Rev Aquac [Internet]. 2018 Aug 1;10(3):738–73. Available from: https://doi.org/10.1111/raq.12200

Mapelli-Brahm P, Gómez-Villegas P, Gonda ML, León-Vaz A, León R, Mildenberger J, et al. Microalgae, Seaweeds and Aquatic Bacteria, Archaea, and Yeasts: Sources of Carotenoids with Potential Antioxidant and Anti-Inflammatory Health-Promoting Actions in the Sustainability Era. Vol. 21, Marine Drugs. 2023.

Galasso C, Corinaldesi C, Sansone C. Carotenoids from Marine Organisms: Biological Functions and Industrial Applications. Antioxidants (Basel, Switzerland). 2017 Nov;6(4).

Mussagy CU, Kot A, Dufossé L, Gonçalves CNDP, Pereira JFB, Santos-Ebinuma VC, et al. Microbial astaxanthin: from bioprocessing to the market recognition. Appl Microbiol Biotechnol. 2023 Jul;107(13):4199–215.

Chou Y-L, Ko C-Y, Yen C-C, Chen L-FO, Shaw J-F. Multiple promoters driving the expression of astaxanthin biosynthesis genes can enhance free-form astaxanthin production. J Microbiol Methods [Internet]. 2019;160:20–8. Available from: https://www.sciencedirect.com/science/article/pii/S0167701218306778

Zhang C-W, Zhang F-L, Dong S-J, He Y-Y, Xu X-M, Peng J, et al. The Discrepancy of Fatty Acid Composition of Astaxanthin Esters and Total Fatty Acids in Photoautotrophic and Heterotrophic Chlorella zofingiensis. J Am Oil Chem Soc [Internet]. 2019 Aug 1;96(8):891–901. Available from: https://doi.org/10.1002/aocs.12230

Gauthier MR, Senhorinho GNA, Scott JA. Microalgae under environmental stress as a source of antioxidants. Algal Res [Internet]. 2020;52:102104. Available from: https://www.sciencedirect.com/science/article/pii/S2211926420309723

Basiony M, Ouyang L, Wang D, Yu J, Zhou L, Zhu M, et al. Optimization of microbial cell factories for astaxanthin production: Biosynthesis and regulations, engineering strategies and fermentation optimization strategies. Synth Syst Biotechnol [Internet]. 2022;7(2):689–704. Available from: https://www.sciencedirect.com/science/article/pii/S2405805X22000023

Ren Y, Deng J, Huang J, Wu Z, Yi L, Bi Y, et al. Using green alga Haematococcus pluvialis for astaxanthin and lipid co-production: Advances and outlook. Bioresour Technol [Internet]. 2021;340:125736. Available from: https://www.sciencedirect.com/science/article/pii/S0960852421010774

Udayan A, Pandey AK, Sirohi R, Sreekumar N, Sang B-I, Sim SJ, et al. Production of microalgae with high lipid content and their potential as sources of nutraceuticals. Phytochem Rev [Internet]. 2023;22(4):833–60. Available from: https://doi.org/10.1007/s11101-021-09784-y

Mularczyk M, Michalak I, Marycz K. Astaxanthin and other Nutrients from Haematococcus pluvialis-Multifunctional Applications. Mar Drugs. 2020 Sep;18(9).

Caramujo M-J, De Carvalho CCCR, Silva SJ, Carman KR. Dietary carotenoids regulate the astaxanthin content of copepods and modulate their susceptibility to UV light and copper toxicity. Mar Drugs. 2012 May;10(5):998–1018.

Kanwugu ON, Ranga Rao A, Ravishankar GA, Glukhareva T V, Kovaleva EG. Chapter 31 - Astaxanthin from bacteria as a feed supplement for animals. In: Ravishankar GA, Ranga Rao ABT-GP on A, editors. Academic Press; 2021. p. 647–67. Available from: https://www.sciencedirect.com/science/article/pii/B9780128233047000209

El Boumlasy S, Mangraviti D, Arena K, Cacciola F, Asraoui F, Debdoubi A. Determination of astaxanthin and astaxanthin esters in three samples of shrimp waste (Parapenaeus longirostris) by high-performance liquid chromatography coupled photo-diode array and mass spectrometry detection. Nat Prod Res. 2023 Aug;1–8.

Panagiotakopoulos I, Karantonis HC, Kartelias IG, Nasopoulou C. Ultrasonic-Assisted Extraction of Astaxanthin from Shrimp By-Products Using Vegetable Oils. Mar Drugs. 2023 Aug;21(9).

Niamnuy C, Devahastin S, Soponronnarit S, Vijaya Raghavan GS. Kinetics of astaxanthin degradation and colour changes of dried shrimp during storage. J Food Eng [Internet]. 2008;87(4):591–600. Available from: https://www.sciencedirect.com/science/article/pii/S0260877408000447

Abdelazim K, Ghit A, Assal D, Dorra N, Noby N, Khattab SN, et al. Production and therapeutic use of astaxanthin in the nanotechnology era. Pharmacol Rep. 2023 Aug;75(4):771–90.

Cirino P, Brunet C, Ciaravolo M, Galasso C, Musco L, Vega Fernández T, et al. The Sea Urchin Arbacia lixula: A Novel Natural Source of Astaxanthin. Mar Drugs. 2017 Jun;15(6).

Stachowiak B, Szulc P. Astaxanthin for the Food Industry. Molecules. 2021 May;26(9).

Valenti MT, Perduca M, Romanelli MG, Mottes M, Dalle Carbonare L. A potential role for astaxanthin in the treatment of bone diseases (Review). Mol Med Rep [Internet]. 2020;22(3):1695–701. Available from: https://doi.org/10.3892/mmr.2020.11284

Brotosudarmo THP, Limantara L, Setiyono E, Heriyanto. Structures of Astaxanthin and Their Consequences for Therapeutic Application. Int J food Sci. 2020;2020:2156582.

Li B, Lee J-Y, Luo Y. Health benefits of astaxanthin and its encapsulation for improving bioavailability: A review. J Agric Food Res [Internet]. 2023;14:100685. Available from: https://www.sciencedirect.com/science/article/pii/S2666154323001928

Rizzardi N, Pezzolesi L, Samorì C, Senese F, Zalambani C, Pitacco W, et al. Natural Astaxanthin Is a Green Antioxidant Able to Counteract Lipid Peroxidation and Ferroptotic Cell Death. Vol. 23, International Journal of Molecular Sciences. 2022.

Budriesi R, Micucci M, Daglia M, Corazza I, Biotti G, Mattioli LB. Chemical Features and Biological Effects of Astaxanthin Extracted from Haematococcus pluvialis Flotow: Focus on Gastrointestinal System. Vol. 12, Biology and Life Sciences Forum. 2022.

Sudharshan SJ, Dyavaiah M. Astaxanthin protects oxidative stress-mediated DNA damage and enhances longevity in Saccharomyces cerevisiae. Biogerontology. 2021 Feb;22(1):81–100.

Kohandel Z, Farkhondeh T, Aschner M, Pourbagher-Shahri AM, Samarghandian S. Anti-inflammatory action of astaxanthin and its use in the treatment of various diseases. Biomed Pharmacother [Internet]. 2022;145:112179. Available from: https://www.sciencedirect.com/science/article/pii/S075333222100963X

Faraone I, Sinisgalli C, Ostuni A, Armentano MF, Carmosino M, Milella L, et al. Astaxanthin anticancer effects are mediated through multiple molecular mechanisms: A systematic review. Pharmacol Res [Internet]. 2020;155:104689. Available from: https://www.sciencedirect.com/science/article/pii/S1043661819327367

Kim SH, Lim JW, Kim H. Astaxanthin Prevents Decreases in Superoxide Dismutase 2 Level and Superoxide Dismutase Activity in Helicobacter pylori-infected Gastric Epithelial Cells. J Cancer Prev. 2019 Mar;24(1):54–8.

Davinelli S, Saso L, D’Angeli F, Calabrese V, Intrieri M, Scapagnini G. Astaxanthin as a Modulator of Nrf2, NF-κB, and Their Crosstalk: Molecular Mechanisms and Possible Clinical Applications. Molecules. 2022 Jan;27(2).

Sun S-Q, Zhao Y-X, Li S-Y, Qiang J-W, Ji Y-Z. Anti-Tumor Effects of Astaxanthin by Inhibition of the Expression of STAT3 in Prostate Cancer. Vol. 18, Marine Drugs. 2020.

Kim H-Y, Kim Y-M, Hong S. Astaxanthin suppresses the metastasis of colon cancer by inhibiting the MYC-mediated downregulation of microRNA-29a-3p and microRNA-200a. Sci Rep [Internet]. 2019;9(1):9457. Available from: https://doi.org/10.1038/s41598-019-45924-3

Kowshik J, Baba AB, Giri H, Deepak Reddy G, Dixit M, Nagini S. Astaxanthin inhibits JAK/STAT-3 signalling to abrogate cell proliferation, invasion and angiogenesis in a hamster model of oral cancer. PLoS One. 2014;9(10):e109114.

Kowshik J, Nivetha R, Ranjani S, Venkatesan P, Selvamuthukumar S, Veeravarmal V, et al. Astaxanthin inhibits hallmarks of cancer by targeting the PI3K/NF-κΒ/STAT3 signalling axis in oral squamous cell carcinoma models. IUBMB Life. 2019 Oct;71(10):1595–610.

Mosier JA, Schwager SC, Boyajian DA, Reinhart-King CA. Cancer cell metabolic plasticity in migration and metastasis. Clin Exp Metastasis. 2021 Aug;38(4):343–59.

Wee P, Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers (Basel). 2017 May;9(5).

Song X, Zhang J, Wang M, Liu W, Gu X, Lv C-J. Astaxanthin induces mitochondria-mediated apoptosis in rat hepatocellular carcinoma CBRH-7919 cells. Biol Pharm Bull. 2011;34(6):839–44.

Hormozi M, Ghoreishi S, Baharvand P. Astaxanthin induces apoptosis and increases the activity of antioxidant enzymes in LS-180 cells. Artif Cells, Nanomedicine, Biotechnol [Internet]. 2019 Dec 4;47(1):891–5. Available from: https://doi.org/10.1080/21691401.2019.1580286

Robertson GS, LaCasse EC, Holcik M. Chapter 18 - Programmed Cell Death. In: Hacker M, Messer W, Bachmann KBT-P, editors. San Diego: Academic Press; 2009. p. 455–73. Available from: https://www.sciencedirect.com/science/article/pii/B978012369521500018X

Si P, Zhu C. Biological and neurological activities of astaxanthin (Review). Mol Med Rep. 2022 Oct;26(4).

Kavitha K, Kowshik J, Kishore TKK, Baba AB, Nagini S. Astaxanthin inhibits NF-κB and Wnt/β-catenin signaling pathways via inactivation of Erk/MAPK and PI3K/Akt to induce intrinsic apoptosis in a hamster model of oral cancer. Biochim Biophys Acta. 2013 Oct;1830(10):4433–44.

Tian Y, Che H, Yang J, Jin Y, Yu H, Wang C, et al. Astaxanthin Alleviates Aflatoxin B1-Induced Oxidative Stress and Apoptosis in IPEC-J2 Cells via the Nrf2 Signaling Pathway. Toxins (Basel). 2023 Mar;15(3).

Wu J, Jiang J, Chen B, Wang K, Tang Y, Liang X. Plasticity of cancer cell invasion: Patterns and mechanisms. Transl Oncol [Internet]. 2021;14(1):100899. Available from: https://www.sciencedirect.com/science/article/pii/S1936523320303910

Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun [Internet]. 2020;11(1):5120. Available from: https://doi.org/10.1038/s41467-020-18794-x

Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, et al. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020 Dec;21(24).

Lee J, Lim JW, Kim H. Astaxanthin Inhibits Matrix Metalloproteinase Expression by Suppressing PI3K/AKT/mTOR Activation in Helicobacter pylori-Infected Gastric Epithelial Cells. Nutrients. 2022 Aug;14(16).

Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB. Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med. 2010 Dec;49(11):1603–16.

Singh N, Baby D, Rajguru JP, Patil PB, Thakkannavar SS, Pujari VB. Inflammation and cancer. Ann Afr Med. 2019;18(3):121–6.

Juan CA, Pérez de la Lastra JM, Plou FJ, Pérez-Lebeña E. The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies. Vol. 22, International Journal of Molecular Sciences. 2021.

Franceschelli S, Pesce M, Ferrone A, De Lutiis MA, Patruno A, Grilli A, et al. Astaxanthin treatment confers protection against oxidative stress in U937 cells stimulated with lipopolysaccharide-reducing O2- production. PLoS One. 2014;9(2):e88359.

Zhang X, Zhao W-E, Hu L, Zhao L, Huang J. Carotenoids inhibit proliferation and regulate expression of peroxisome proliferators-activated receptor gamma (PPARγ) in K562 cancer cells. Arch Biochem Biophys. 2011 Aug;512(1):96–106.

Gholami H, Abbasalipourkabir R, Ziamajidi N, Divsalar A, Saeidifar M, Zarei S. The Effect of Beta-lactoglobulin Nanocapsules Containing Astaxanthin and 5-fluorouracil on the Antioxidant Enzymes Activity of Superoxide Dismutase, Catalase and Glutathione Peroxidase in HCT116 Colorectal Cancer Cell Line [Internet]. Vol. 18, Current Drug Therapy. p. 407–14. Available from: https://www.ingentaconnect.com/content/ben/cdth/2023/00000018/00000005/art00006

Chang MX, Xiong F. Astaxanthin and its Effects in Inflammatory Responses and Inflammation-Associated Diseases: Recent Advances and Future Directions. Molecules. 2020 Nov;25(22).

Priyadarshini L, Aggarwal A. Astaxanthin inhibits cytokines production and inflammatory gene expression by suppressing IκB kinase-dependent nuclear factor κB activation in pre and postpartum Murrah buffaloes during different seasons. Vet world. 2018 Jun;11(6):782–8.

Taştan Bal T, Akaras N, Demir Ö, Ugan RA. Protective effect of astaxanthin and metformin in the liver of rats in which the polycystic ovary syndrome model was formed by giving letrozole. Iran J Basic Med Sci. 2023;26(6):688–94.

Pereira CPM, Souza ACR, Vasconcelos AR, Prado PS, Name JJ. Antioxidant and anti‑inflammatory mechanisms of action of astaxanthin in cardiovascular diseases (Review). Int J Mol Med. 2021 Jan;47(1):37–48.

Kishimoto Y, Tani M, Uto-Kondo H, Iizuka M, Saita E, Sone H, et al. Astaxanthin suppresses scavenger receptor expression and matrix metalloproteinase activity in macrophages. Eur J Nutr. 2010 Mar;49(2):119–26.

Lee S-J, Bai S-K, Lee K-S, Namkoong S, Na H-J, Ha K-S, et al. Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I(kappa)B kinase-dependent NF-kappaB activation. Mol Cells. 2003 Aug;16(1):97–105.

Block KI, Gyllenhaal C, Lowe L, Amedei A, Amin ARMR, Amin A, et al. Designing a broad-spectrum integrative approach for cancer prevention and treatment. Semin Cancer Biol [Internet]. 2015;35:S276–304. Available from: https://www.sciencedirect.com/science/article/pii/S1044579X15000887

Ono A, Sekita K, Saitoh M, Umemura T, Ogawa Y, Furuya T, et al. [A 13-week subchronic oral toxicity study of haematococcus colour in F344 rats]. Kokuritsu Iyakuhin Shokuhin Eisei Kenkyujo hokoku = Bull Natl Inst Heal Sci. 1999;(117):91–8.

Stewart JS, Lignell Å, Pettersson A, Elfving E, Soni MG. Safety assessment of astaxanthin-rich microalgae biomass: Acute and subchronic toxicity studies in rats. Food Chem Toxicol [Internet]. 2008;46(9):3030–6. Available from: https://www.sciencedirect.com/science/article/pii/S0278691508002895

Jannel S, Caro Y, Bermudes M, Petit T. Novel Insights into the Biotechnological Production of Haematococcus pluvialis-Derived Astaxanthin: Advances and Key Challenges to Allow Its Industrial Use as Novel Food Ingredient. Vol. 8, Journal of Marine Science and Engineering. 2020.

Mao JJ, Pillai GG, Andrade CJ, Ligibel JA, Basu P, Cohen L, et al. Integrative oncology: Addressing the global challenges of cancer prevention and treatment. CA Cancer J Clin [Internet]. 2022 Mar 1;72(2):144–64. Available from: https://doi.org/10.3322/caac.21706

Landon R, Gueguen V, Petite H, Letourneur D, Pavon-Djavid G, Anagnostou F. Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications. Vol. 18, Marine Drugs. 2020.