Pelargonidin, a Dietary Anthocyanidin in the Prevention of Colorectal Cancer and Its Chemoprotective Mechanisms

  • Manju Vaiyapuri
  • Srivalli Thimmarayan
  • Madhusmitha Dhupal
  • Harikrishna Reddy Rallabandi
  • Manjulatha Mekapogu
  • Bala Murali Krishna Vasamsetti
  • Mallappa Kumara Swamy
  • Karthi Natesan


Diseases of bowl wall mucosa stemming from sudden mutation lead to the development of colorectal cancer (CRC) cells by the transformation of normal epithelial cells into neoplastic lesions. CRC is considered to be a global burden; hence, its incidence rate is expeditiously increased up to ten-fold higher, worldwide. The epidemiological report pinpointed CRC as the utmost third common malignancy in men and second in women. Because of greater efficacy, the synthetic drugs are unsatisfactory due to higher toxic effects to the normal cells, and a chance of developing multidrug resistance by tumor cells. Therefore, dietary flavonoids with potent anticarcinogenic effects have been focused on recent investigations. Pelargonidin (PD), a bioactive molecule classified under anthocyanidin is present in red and pink pigmented berries. PD efficiently modulates intercellular antioxidant status, thereby reducing oxidative DNA damage, cellular proliferation, differentiation, apoptosis, angiogenesis, and reverse drug resistance of metastatic cells, and potentially induces cell cycle arrest, thereby interfering in colorectal carcinogenesis. PD scavenges and normalizes the intracellular reactive oxygen species (ROS), which results in gene mutation and induction of colon carcinogenesis. Therefore, the proliferation of tumor cells would be affected or blocked potentially due to disturbance in cell cycle protein by these ROS. Considering the wide pharmacological benefits of PD, this chapter deliberately reviews the cumulative research data from in vitro human colon cancer cell line studies on chemoprotective property of PD against CRC, and also summarizes the underlying mechanism in experimental models.


Colorectal cancer (CRC) Pelargonidin Antioxidant Apoptosis Chemoprevention 


  1. Abraham SK, Schupp N, Schmid U, Stopper H (2007) Antigenotoxic effects of the phytoestrogen pelargonidin chloride and the polyphenol chlorogenic acid. Mol Nutri Food Res 51(7):880–887Google Scholar
  2. Adams JM (2003) Ways of dying: multiple pathways to apoptosis. Genes Dev 17(20):2481–2495PubMedGoogle Scholar
  3. Akhtar MS, Swamy MK (eds) (2018) Anticancer plants: properties and application. Springer, SingaporeGoogle Scholar
  4. Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F (2017) Global patterns and trends in colorectal cancer incidence and mortality. Gut 66(4):683–691Google Scholar
  5. Ashktorab H, Belgrave K, Hosseinkhah F, Brim H, Nouraie M, Takkikto M, Hewitt S, Lee EL, Dashwood R, Smoot D (2009) Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma. Dig Dis Sci 54(10):2109PubMedGoogle Scholar
  6. Aswar M, Aswar U, Wagh A, Watkar B, Vyas M, Gujar KN (2008) Antimicrobial activity of Ficus benghalensis. Pharmacol Online 2:715–725Google Scholar
  7. Augusti K, Daniel RS, Cherian S, Sheela C, Nair C (1994) Effect of leucopelargonin derivative from Ficus bengalensis Linn. on diabetic dogs. Ind J Med Res 99:82–86Google Scholar
  8. Bardhan K, Liu K (2013) Epigenetics and colorectal cancer pathogenesis. Cancers 5(2):676–713PubMedPubMedCentralGoogle Scholar
  9. Barnes JS, Schug KA (2011a) Structural characterization of cyanidin-3,5-diglucoside and pelargonidin-3,5-diglucoside anthocyanins: Multi-dimensional fragmentation pathways using high performance liquid chromatography-electrospray ionization-ion trap-time of flight mass spectrometry. Int J Mass Spectrom 308(1):71–80Google Scholar
  10. Beekwilder J, Jonker H, Meesters P, Hall RD, van der Meer IM, Ric de Vos C (2005) Antioxidants in raspberry: on-line analysis links antioxidant activity to a diversity of individual metabolites. J Agric Food Chem 53(9):3313–3320Google Scholar
  11. Bruyère C, Meijer L (2013) Targeting cyclin-dependent kinases in anti-neoplastic therapy. Curr Opin Cell Biol 25(6):772–779PubMedGoogle Scholar
  12. Bub A, Watzl B, Heeb D, Rechkemmer G, Briviba K (2001) Malvidin-3-glucoside bioavailability in humans after ingestion of red wine, dealcoholized red wine and red grape juice. Eur J Nutri 40(3):113–120Google Scholar
  13. Čipak gašparović A, Lovaković T, Žarković N (2010) Oxidative stress and antioxidants: biological response modifiers of oxidative homeostasis in cancer. Period Biol 112(4):433–439Google Scholar
  14. Datir SS (2018) Plant metabolites as new leads to anticancer drug discovery: approaches and challenges. In: Anticancer plants: natural products and biotechnological implements. Springer, Singapore, pp 141–161Google Scholar
  15. Dickinson DA, Forman HJ (2002) Cellular glutathione and thiols metabolism. Biochem Pharmacol 64(5–6):1019–1026PubMedGoogle Scholar
  16. Ďuračková Z (2010) Some current insights into oxidative stress. Physiol Res 59(4)Google Scholar
  17. Felgines C, Talavera S, Texier O, Gil-Izquierdo A, Lamaison J-L, Remesy C (2005) Blackberry anthocyanins are mainly recovered from urine as methylated and glucuronidated conjugates in humans. J Agricult Food Chem 53(20):7721–7727Google Scholar
  18. Felgines C, Texier O, Besson C, Lyan B, Lamaison J-L, Scalbert A (2007) Strawberry pelargonidin glycosides are excreted in urine as intact glycosides and glucuronidated pelargonidin derivatives in rats. Br J Nutri 98(6):1126–1131Google Scholar
  19. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136(5):E359–E386Google Scholar
  20. Ferretti G, Bacchetti T, Belleggia A, Neri D (2010) Cherry antioxidants: from farm to table. Molecules 15(10):6993–7005PubMedPubMedCentralGoogle Scholar
  21. Fimia GM, Piacentini M (2010) Regulation of autophagy in mammals and its interplay with apoptosis. Cell Mol Life Sci 67(10):1581–1588PubMedGoogle Scholar
  22. Floyd RA, Watson JJ, Wong PK, Altmiller DH, Rickard RC (1986) Hydroxyl free radical adduct of deoxyguanosine: sensitive detection and mechanisms of formation. Free Rad Res Commun 1(3):163–172Google Scholar
  23. Frank T, Netzel M, Strass G, Bitsch R, Bitsch I (2003) Bioavailability of anthocyanidin-3-glucosides following consumption of red wine and red grape juice. Can J Physiol Pharmacol 81(5):423–435PubMedGoogle Scholar
  24. Gingras D, Béliveau R (2011) Colorectal cancer prevention through dietary and lifestyle modifications. Cancer Microenviron 4(2):133–139PubMedPubMedCentralGoogle Scholar
  25. Graham KA, Kulawiec M, Owens KM, Li X, Desouki MM, Chandra D, Singh KK (2010) NADPH oxidase 4 is an oncoprotein localized to mitochondria. Cancer Biol Ther 10(3):223–231PubMedPubMedCentralGoogle Scholar
  26. Halliwell B (1994) Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 344(8924):721–724PubMedGoogle Scholar
  27. Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediat Inflam 2007:1–10Google Scholar
  28. Hippeli S, Heiser I, Elstner EF (1999) Activated oxygen and free oxygen radicals in pathology: new insights and analogies between animals and plants. Plant Physiol Biochem 37(3):167–178Google Scholar
  29. Hou D-X, Yanagita T, Uto T, Masuzaki S, Fujii M (2005) Anthocyanidins inhibit cyclooxygenase-2 expression in LPS-evoked macrophages: structure–activity relationship and molecular mechanisms involved. Biochem Pharmacol 70(3):417–425PubMedGoogle Scholar
  30. Jass JR (2007) Molecular heterogeneity of colorectal cancer: implications for cancer control. Surg Oncol 16:7–9Google Scholar
  31. Karthi N, Kalaiyarasu T, Kandakumar S, Mariyappan P, Manju V (2016) Pelargonidin induces apoptosis and cell cycle arrest via a mitochondria mediated intrinsic apoptotic pathway in HT29 cells. RSC Adv 6(51):45064–45076Google Scholar
  32. Klaunig JE, Wang Z, Pu X, Zhou S (2011) Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 254(2):86–99Google Scholar
  33. Lee K-J, Inoue M, Otani T, Iwasaki M, Sasazuki S, Tsugane S, Group JS (2007) Physical activity and risk of colorectal cancer in Japanese men and women: the Japan Public Health Center-Based Prospective Study. Cancer Causes Contr 18(2):199–209Google Scholar
  34. Mahomoodally MF, Gurib-Fakim A, Subratty AH (2005) Antimicrobial activities and phytochemical profiles of endemic medicinal plants of Mauritius. Pharm Biol 43(3):237–242Google Scholar
  35. Miller PE, Lazarus P, Lesko SM, Cross AJ, Sinha R, Laio J, Zhu J, Harper G, Muscat JE, Hartman TJ (2013) Meat-related compounds and colorectal cancer risk by anatomical subsite. Nutri Cancer 65(2):202–226Google Scholar
  36. Mullen W, Edwards CA, Serafini M, Crozier A (2008) Bioavailability of pelargonidin-3-O-glucoside and its metabolites in humans following the ingestion of strawberries with and without cream. J Agri Food Chem 56(3):713–719Google Scholar
  37. Neergheen VS, Bahorun T, Taylor EW, Jen L-S, Aruoma OI (2010) Targeting specific cell signaling transduction pathways by dietary and medicinal phytochemicals in cancer chemoprevention. Toxicology 278(2):229–241PubMedGoogle Scholar
  38. Nikkhah E, Khayami M, Heidari R (2008) In vitro screening for antioxidant activity and cancer suppressive effect of Blackberry (Morus nigra). Iran J Cancer Prev 1:167–172Google Scholar
  39. Noda N, Wakasugi H (2001) Cancer and oxidative stress. Jpn Med Ass J 44(12):535–539Google Scholar
  40. Nosho K, Irahara N, Shima K, Kure S, Kirkner GJ, Schernhammer ES, Hazra A, Hunter DJ, Quackenbush J, Spiegelman D (2008) Comprehensive biostatistical analysis of CpG island methylator phenotype in colorectal cancer using a large population-based sample. PLoS One 3(11):e3698PubMedPubMedCentralGoogle Scholar
  41. Ouakrim DA, Pizot C, Boniol M, Malvezzi M, Boniol M, Negri E, Bota M, Jenkins MA, Bleiberg H, Autier P (2015) Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database. BMJ 351:h4970Google Scholar
  42. Palou G, Palou R, Guerra-Moreno A, Duch A, Travesa A, Quintana DG (2010) Cyclin regulation by the s phase checkpoint. J Biol Chem 285(34):26431–26440PubMedPubMedCentralGoogle Scholar
  43. Pergola C, Rossi A, Dugo P, Cuzzocrea S, Sautebin L (2006) Inhibition of nitric oxide biosynthesis by anthocyanin fraction of blackberry extract. Nitric Oxide 15(1):30–39PubMedGoogle Scholar
  44. Pradelli L, Beneteau M, Chauvin C, Jacquin M, Marchetti S, Munoz-Pinedo C, Auberger P, Pende M, Ricci J (2010) Glycolysis inhibition sensitizes tumor cells to death receptors-induced apoptosis by AMP kinase activation leading to Mcl-1 block in translation. Oncogene 29(11):1641PubMedGoogle Scholar
  45. Raju J, Patlolla JM, Swamy MV, Rao CV (2004) Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells. Cancer Epidemiol Prevent Biomarkers 13(8):1392–1398Google Scholar
  46. Ramos S (2007) Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J Nutri Biochem 18(7):427–442Google Scholar
  47. Ravichandra VD, Ramesh C, Swamy MK, Purushotham B, Rudramurthy GR (2018) Anticancer plants: chemistry, pharmacology, and potential applications. In: Anticancer plants: properties and application. Springer, Singapore, pp 485–515Google Scholar
  48. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Rad Biol Med 49(11):1603–1616PubMedGoogle Scholar
  49. Singh A, Tripathi P (2018) Potential of natural products for the prevention of oral cancer. In: Anticancer plants: natural products and biotechnological implements. Springer, Singapore, pp 41–66Google Scholar
  50. Sivalokanathan S, Ilayaraja M, Balasubramanian MP (2006) Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats. Mol Cell Biochem 281(1–2):87Google Scholar
  51. Smith A, Simanski S, Fallahi M, Ayad NG (2007) Redundant ubiquitin ligase activities regulate wee1 degradation and mitotic entry. Cell Cycle 6(22):2795–2799PubMedGoogle Scholar
  52. Tanaka T (2009) Colorectal carcinogenesis: review of human and experimental animal studies. J Carcinogen 8:5Google Scholar
  53. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108PubMedGoogle Scholar
  54. Tsuda T, Horio F, Uchida K, et al. (2003) Dietary cyanidin 3-O-β-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J Nutr 133(7):2125–2130.Google Scholar
  55. Valadez-Vega C, Delgado-Olivares L, González JAM, García EA, Ibarra JRV, Moreno ER, Gutiérrez MS, Martínez MTS, Clara ZP, Ramos ZC (2013) The role of natural antioxidants in cancer disease. In: Oxidative stress and chronic degenerative diseases-a role for antioxidants. IntechOpen, London.Google Scholar
  56. Wang H, Nair MG, Strasburg GM, Chang Y-C, Booren AM, Gray JI, DeWitt DL (1999) Antioxidant and antiinflammatory activities of anthocyanins and their aglycon, cyanidin, from tart cherries. J Nat Prod 62(2):294–296PubMedGoogle Scholar
  57. Wang JJ, Shi QH, Zhang W, Sanderson BJ (2012) Anti-skin cancer properties of phenolic-rich extract from the pericarp of mangosteen (Garcinia mangostana Linn.). Food Chem Toxicol 50(9):3004–3013PubMedGoogle Scholar
  58. Wu X, Beecher GR, Holden JM, Haytowitz DB, Gebhardt SE, Prior RL (2006) Concentrations of anthocyanins in common foods in the United States and estimation of normal consumption. J Agric Food Chem 54(11):4069–4075PubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  • Manju Vaiyapuri
    • 1
  • Srivalli Thimmarayan
    • 1
  • Madhusmitha Dhupal
    • 2
  • Harikrishna Reddy Rallabandi
    • 3
  • Manjulatha Mekapogu
    • 4
  • Bala Murali Krishna Vasamsetti
    • 5
  • Mallappa Kumara Swamy
    • 6
  • Karthi Natesan
    • 1
    • 7
  1. 1.Cell and Molecular Biology Lab, Department of BiochemistryPeriyar UniversitySalemIndia
  2. 2.Department of Microbiology and Global Biomedical SciencesWonju College of Medicine, Yonsei UniversityWonjuSouth Korea
  3. 3.Animal Biotechnology DivisionNational Institute of Animal Science, RDAWanjuSouth Korea
  4. 4.Floriculture Research DivisionNational Institute of Horticulture and Herbal Sciences, RDAWanjuSouth Korea
  5. 5.Chemical Safety Division, Department of Agro-food Safety and Crop ProtectionNational Institute of Agricultural Sciences, RDAWanjuSouth Korea
  6. 6.Department of BiotechnologyEast West First Grade CollegeBengaluruIndia
  7. 7.Genomic DivisionNational Academy of Agricultural Science, RDAJeonjuSouth Korea

Personalised recommendations