Skip to main content

Advertisement

SpringerLink
Log in

Chemopreventive aspects, investigational anticancer applications and current perspectives on allyl isothiocyanate (AITC): a review

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Allyl isothiocyanates (AITC) have gained recognition in recent years as effective chemotherapeutic and epigenetic modulators. The chemopreventive properties and toxicological perspectives of AITCs from the last few decades were taken into account by a number of investigations. Their active therapeutic relevance was hindered by a number of factors, including instability under typical physiological conditions and low bioavailability due to low aqueous solubility. In this review, we highlighted the chemopreventive attributes of AITC in relation to its molecular mechanisms and metabolic fate for cancer. Moreover, we emphasized on investigational anticancer activities and various strategies for delivery of AITC in different types of cancer. Considering cellular interactions, we shed light on the toxicological properties of AITCs to address further issues regarding their assessment in therapeutic development. This review identifies knowledge gaps with various contemporary approaches involving most recent studies and may pave the way for a better understanding for the development of novel AITC therapeutics.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

All data available in a submitted manuscript.

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin 68:394–424. https://doi.org/10.3322/caac.21492

    Article  Google Scholar 

  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin 71:209–249

    Article  Google Scholar 

  3. Koehn FE (2012) Natural products and cancer drug discovery. Springer Science & Business Media

    Google Scholar 

  4. Hu Y, Chen J, Hu G, Yu J, Zhu X, Lin Y, Chen S, Yuan J (2015) Statistical research on the bioactivity of new marine natural products discovered during the 28 years from 1985 to 2012. Mar Drugs 13:202–221. https://doi.org/10.3390/md13010202

    Article  PubMed Central  PubMed  Google Scholar 

  5. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981–2002. J Nat Prod 66:1022–1037

    Article  CAS  PubMed  Google Scholar 

  7. Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B (2017) The different mechanisms of cancer drug resistance: a brief review. Adv Pharma Bull 7:339. https://doi.org/10.15171/apb.2017.041

    Article  CAS  Google Scholar 

  8. Bukowski K, Kciuk M, Kontek R (2020) Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci 21:3233. https://doi.org/10.3390/ijms21093233

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Cuellar-Nuñez ML, Luzardo-Ocampo I, Lee-Martínez S, Larrauri-Rodríguez M, Zaldívar-Lelo de Larrea G, Pérez-Serrano RM, Camacho-Calderón N (2022) Isothiocyanate-rich extracts from cauliflower (Brassica oleracea Var Botrytis) and radish (Raphanus sativus) inhibited metabolic activity and induced ROS in selected human HCT116 and HT-29 colorectal cancer cells. Int J Environ Res Public Health 19:14919

    Article  PubMed Central  PubMed  Google Scholar 

  10. Charron CS, Clevidence BA, Albaugh GA, Kramer MH, Vinyard BT, Milner JA, Novotny JA (2013) Assessment of DNA damage and repair in adults consuming allyl isothiocyanate or Brassica vegetables. J Nutr Biochem 24:894–902

    Article  CAS  PubMed  Google Scholar 

  11. Verhoeven DT, Goldbohm RA, van Poppel G, Verhagen H, van den Brandt PA (1996) Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol Prev Biomarkers 5:733–748

    CAS  Google Scholar 

  12. Wu X, Huang H, Childs H, Wu Y, Yu L, Pehrsson PR (2021) Glucosinolates in Brassica vegetables: characterization and factors that influence distribution, content, and intake. Annu Rev Food Sci Technol 12:485–511

    Article  CAS  PubMed  Google Scholar 

  13. Mithen RF, Dekker M, Verkerk R, Rabot S, Johnson IT (2000) The nutritional significance, biosynthesis and bioavailability of glucosinolates in human foods. J Sci Food Agric 80:967–984

    Article  CAS  Google Scholar 

  14. Cheung KL, Kong A-N (2010) Molecular targets of dietary phenethyl isothiocyanate and sulforaphane for cancer chemoprevention. AAPS J 12:87–97. https://doi.org/10.1208/s12248-009-9162-8

    Article  CAS  PubMed  Google Scholar 

  15. Jakubikova J, Bao Y, Sedlak J (2005) Isothiocyanates induce cell cycle arrest, apoptosis and mitochondrial potential depolarization in HL-60 and multidrug-resistant cell lines. Anticancer Res 25:3375–3386

    CAS  PubMed  Google Scholar 

  16. Fimognari C, Lenzi M, Hrelia P (2009) Apoptosis induction by sulfur-containing compounds in malignant and nonmalignant human cells. Environ Mol Mutagen 50:171–189

    Article  CAS  PubMed  Google Scholar 

  17. Ioannides C, Konsue N (2015) A principal mechanism for the cancer chemopreventive activity of phenethyl isothiocyanate is modulation of carcinogen metabolism. Drug Metab Rev 47:356–373

    Article  CAS  PubMed  Google Scholar 

  18. Chiang JH, Tsai FJ, Hsu YM, Yin MC, Chiu HY, Yang JS (2020) Sensitivity of allyl isothiocyanate to induce apoptosis via ER stress and the mitochondrial pathway upon ROS production in colorectal adenocarcinoma cells. Oncol Rep 44:1415–1424

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Chang P-y, Tsai F-j, Bau D-t, Hsu Y-m, Yang J-s, M-g Tu, Chiang S-l (2021) Potential effects of allyl isothiocyanate on inhibiting cellular proliferation and inducing apoptotic pathway in human cisplatin-resistant oral cancer cells. J Formos Med Assoc 120:515–523

    Article  CAS  PubMed  Google Scholar 

  20. Liao C-L, Peng S-F, Chen J-C, Chen P-Y, Huang A-C, Lien J-C, Chueh F-S, Chiang T-A, Wu P-P, Lin K-I (2021) Allyl isothiocyanate induces DNA damage and impairs DNA repair in human breast cancer MCF-7 cells. Anticancer Res 41:4343–4351

    Article  CAS  PubMed  Google Scholar 

  21. Caglayan B, Kilic E, Dalay A, Altunay S, Tuzcu M, Erten F, Orhan C, Gunal MY, Yulug B, Juturu V (2019) Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice. Mol Biol Rep 46:241–250

    Article  CAS  PubMed  Google Scholar 

  22. Chen N-G, Chen K-T, Lu C-C, Lan Y-H, Lai C-H, Chung Y-T, Yang J-S, Lin Y-C (2010) Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma GBM 8401 cells through a mitochondria-dependent pathway. Oncol Rep 24:449–455

    CAS  PubMed  Google Scholar 

  23. Ling X, Westover D, Cao F, Cao S, He X, Kim H-R, Zhang Y, Chan DC, Li F (2015) Synergistic effect of allyl isothiocyanate (AITC) on cisplatin efficacy in vitro and in vivo. Am J Cancer Res 5:2516

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Wang Q, Bao Y (2021) Nanodelivery of natural isothiocyanates as a cancer therapeutic. Free Radical Biol Med 167:125–140

    Article  CAS  Google Scholar 

  25. Navarro SL, Li F, Lampe JW (2011) Mechanisms of action of isothiocyanates in cancer chemoprevention: an update. Food Funct 2:579–587

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Tarar A, Alyami EM, Peng C-A (2022) Eradication of myrosinase-tethered cancer cells by allyl isothiocyanate derived from enzymatic hydrolysis of sinigrin. Pharmaceutics 14:144

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Baspinar Y, Elmaci I, Ozpinar A, Altinoz MA (2020) Long non-coding RNA MALAT1 as a key target in pathogenesis of glioblastoma: Janus faces or Achilles’ heal? Gene 739:144518

    Article  CAS  PubMed  Google Scholar 

  28. Sundaram MK, Preetha R, Haque S, Akhter N, Khan S, Ahmed S, Hussain A (2021) Dietary isothiocyanates inhibit cancer progression by modulation of epigenome. Sem Cancer Biol 83:353–376

    Article  Google Scholar 

  29. Bhattacharya A, Li Y, Wade KL, Paonessa JD, Fahey JW, Zhang Y (2010) Allyl isothiocyanate-rich mustard seed powder inhibits bladder cancer growth and muscle invasion. Carcinogenesis 31:2105–2110

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Bhattacharya A, Tang L, Li Y, Geng F, Paonessa JD, Chen SC, Wong MK, Zhang Y (2010) Inhibition of bladder cancer development by allyl isothiocyanate. Carcinogenesis 31:281–286

    Article  CAS  PubMed  Google Scholar 

  31. Savio ALV, da Silva GN, de Camargo EA, Salvadori DMF (2014) Cell cycle kinetics, apoptosis rates, DNA damage and TP53 gene expression in bladder cancer cells treated with allyl isothiocyanate (mustard essential oil). Mutation Res/Fundamental Mol Mech Mutagen 762:40–46

    Article  CAS  Google Scholar 

  32. Sávio ALV, da Silva GN, Salvadori DMF (2015) Inhibition of bladder cancer cell proliferation by allyl isothiocyanate (mustard essential oil). Mutation Res/Fundamental Mol Mech Mutagen 771:29–35

    Article  Google Scholar 

  33. Chang WJ, Chen BH, Inbaraj BS, Chien JT (2019) Preparation of allyl isothiocyanate nanoparticles, their anti-inflammatory activity towards RAW 264.7 macrophage cells and anti-proliferative effect on HT1376 bladder cancer cells. J Sci Food Agric 99:3106–3116

    Article  CAS  PubMed  Google Scholar 

  34. Jiang Z, Liu X, Chang K, Liu X, Xiong J (2016) Allyl isothiocyanate inhibits the proliferation of renal carcinoma cell line GRC-1 by inducing an imbalance between Bcl2 and Bax. Med Sci Monit 22:4283

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Rutz J, Maxeiner S, Grein T, Sonnenburg M, Khadir SE, Makhatelashvili N, Mann J, Xie H, Cinatl J, Thomas A (2022) Allyl-, butyl-and phenylethyl-isothiocyanate modulate Akt–mTOR and cyclin–CDK signaling in gemcitabine-and cisplatin-resistant bladder cancer cell lines. Int J Mol Sci 23:10996

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Tseng E, Ramsay EAS, Morris ME (2004) Dietary organic isothiocyanates are cytotoxic in human breast cancer MCF-7 and mammary epithelial MCF-12A cell lines. Exp Biol Med 229:835–842

    Article  CAS  Google Scholar 

  37. Singletary K, MacDonald C (2000) Inhibition of benzo [a] pyrene-and 1, 6-dinitropyrene-DNA adduct formation in human mammary epithelial cells bydibenzoylmethane and sulforaphane. Cancer Lett 155:47–54

    Article  CAS  PubMed  Google Scholar 

  38. Kumar A, D’Souza SS, Tickoo S, Salimath BP, Singh H (2009) Antiangiogenic and proapoptotic activities of allyl isothiocyanate inhibit ascites tumor growth in vivo. Integr Cancer Ther 8:75–87

    Article  CAS  PubMed  Google Scholar 

  39. Bodo J, Chovancova J, Hunakova L, Sedlak J (2005) Enhanced sensitivity of human ovarian carcinoma cell lines A2780 and A2780/CP to the combination of cisplatin and synthetic isothiocyanate ethyl 4-isothiocyanatobutanoate. Neoplasma 52:510

    CAS  PubMed  Google Scholar 

  40. Wang X, Govind S, Sajankila SP, Mi L, Roy R, Chung FL (2011) Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin. Mol Nutr Food Res 55:1572–1581

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Kim M, Cho HJ, Kwon GT, Kang YH, Kwon SH, Her S, Park T, Kim Y, Kee Y, Park JHY (2015) Benzyl isothiocyanate suppresses high-fat diet-stimulated mammary tumor progression via the alteration of tumor microenvironments in obesity-resistant BALB/c mice. Mol Carcinog 54:72–82

    Article  CAS  PubMed  Google Scholar 

  42. Kim EJ, Hong JE, Eom SJ, Lee J-Y, Park JHY (2011) Oral administration of benzyl-isothiocyanate inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. Breast Cancer Res Treat 130:61–71

    Article  CAS  PubMed  Google Scholar 

  43. Bao C, Kim MC, Chen J, Song J, Ko HW, Lee HJ (2016) Sulforaphene interferes with human breast cancer cell migration and invasion through inhibition of hedgehog signaling. J Agric Food Chem 64:5515–5524

    Article  CAS  PubMed  Google Scholar 

  44. Zhang Z, Atwell LL, Farris PE, Ho E, Shannon J (2016) Associations between cruciferous vegetable intake and selected biomarkers among women scheduled for breast biopsies. Public Health Nutr 19:1288–1295

    Article  PubMed  Google Scholar 

  45. Rajakumar T, Pugalendhi P, Thilagavathi S (2018) Protective effect of allyl isothiocyanate on glycoprotein components in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in rats. Indian J Clin Biochem 33:171–177

    Article  CAS  PubMed  Google Scholar 

  46. Rajakumar T, Pugalendhi P, Thilagavathi S, Ananthakrishnan D, Gunasekaran K (2018) Allyl isothiocyanate, a potent chemopreventive agent targets AhR/Nrf2 signaling pathway in chemically induced mammary carcinogenesis. Mol Cell Biochem 437:1–12

    Article  CAS  PubMed  Google Scholar 

  47. Jiang Z, Dong B, Chen B, Wang J, Xu L, Zhang S, Song H (2013) Multifunctional Au@ mSiO2/rhodamine B isothiocyanate nanocomposites: cell imaging, photocontrolled drug release, and photothermal therapy for cancer cells. Small 9:604–612

    Article  CAS  PubMed  Google Scholar 

  48. Herz C, Hertrampf A, Zimmermann S, Stetter N, Wagner M, Kleinhans C, Erlacher M, Schüler J, Platz S, Rohn S (2014) The isothiocyanate erucin abrogates telomerase in hepatocellular carcinoma cells in vitro and in an orthotopic xenograft tumour model of HCC. J Cell Mol Med 18:2393–2403

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Zhang Q-c, Pan Z-h, Liu B-n, Meng Z-w, Wu X, Q-h Z, Xu K (2017) Benzyl isothiocyanate induces protective autophagy in human lung cancer cells through an endoplasmic reticulum stress-mediated mechanism. Acta Pharmacol Sin 38:539–550

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Liu P, Behray M, Wang Q, Wang W, Zhou Z, Chao Y, Bao Y (2018) Anti-cancer activities of allyl isothiocyanate and its conjugated silicon quantum dots. Sci Rep 8:1–11

    Google Scholar 

  51. Rakariyatham K, Yang X, Gao Z, Song M, Han Y, Chen X, Xiao H (2019) Synergistic chemopreventive effect of allyl isothiocyanate and sulforaphane on non-small cell lung carcinoma cells. Food Funct 10:893–902

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Ahmed AG, Hussein UK, Ahmed AE, Kim KM, Mahmoud HM, Hammouda O, Jang KY, Bishayee A (2020) Mustard seed (Brassica nigra) extract exhibits antiproliferative effect against human lung cancer cells through differential regulation of apoptosis, cell cycle, migration, and invasion. Molecules 25:2069

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Mitsiogianni M, Mantso T, Trafalis DT, Vasantha Rupasinghe H, Zoumpourlis V, Franco R, Botaitis S, Pappa A, Panayiotidis MI (2020) Allyl isothiocyanate regulates lysine acetylation and methylation marks in an experimental model of malignant melanoma. Eur J Nutr 59:557–569

    Article  CAS  PubMed  Google Scholar 

  54. Lu K-W, Lu T-J, Chueh F-S, Lai K-C, Hsia T-C, Peng S-F, Cheng C-C, Chou Y-C, Hsu F-T (2022) Allyl isothiocyanate (AITC) induces apoptotic cell death in vitro and exhibits anti-tumor activity in a human glioblastoma GBM8401/luc2 model. Int J Mol Sci 23:10411

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Ko JA, Jeon JY, Park HJ (2012) Preparation and characterization of allyl isothiocyanate microcapsules by spray drying. J Food Biochem 36:255–261

    Article  CAS  Google Scholar 

  56. Kumar G, Tuli HS, Mittal S, Shandilya JK, Tiwari A, Sandhu SS (2015) Isothiocyanates: a class of bioactive metabolites with chemopreventive potential. Tumor Biology 36:4005–4016

    Article  CAS  PubMed  Google Scholar 

  57. Liu TT, Yang TS (2010) Stability and antimicrobial activity of allyl isothiocyanate during long-term storage in an oil-in-water emulsion. J Food Sci 75:C445–C451

    Article  CAS  PubMed  Google Scholar 

  58. Zhang Q-F, Jiang Z-T, Li R (2007) Complexation of allyl isothiocyanate with β-cyclodextrin and its derivatives and molecular microcapsule of allyl isothiocyanate in β-cyclodextrin. Eur Food Res Technol 225:407–413

    Article  CAS  Google Scholar 

  59. Zhang Z-Q, Pan C-H, Chung D (2011) Tannic acid cross-linked gelatin–gum arabic coacervate microspheres for sustained release of allyl isothiocyanate: characterization and in vitro release study. Food Res Int 44:1000–1007

    Article  Google Scholar 

  60. Pandey A, Dhas N, Deshmukh P, Caro C, Patil P, García-Martín ML, Padya B, Nikam A, Mehta T, Mutalik S (2020) Heterogeneous surface architectured metal-organic frameworks for cancer therapy, imaging, and biosensing: a state-of-the-art review. Coord Chem Rev 409:213212

    Article  CAS  Google Scholar 

  61. Lashkari E, Wang H, Liu L, Li J, Yam K (2017) Innovative application of metal-organic frameworks for encapsulation and controlled release of allyl isothiocyanate. Food Chem 221:926–935

    Article  CAS  PubMed  Google Scholar 

  62. Encinas-Basurto D, Ibarra J, Juarez J, Burboa MG, Barbosa S, Taboada P, Troncoso-Rojas R, Valdez MA (2017) Poly (lactic-co-glycolic acid) nanoparticles for sustained release of allyl isothiocyanate: Characterization, in vitro release and biological activity. J Microencapsul 34:231–242

    Article  CAS  PubMed  Google Scholar 

  63. Zhang Z, Garzotto M, Davis EW, Mori M, Stoller WA, Farris PE, Wong CP, Beaver LM, Thomas GV, Williams DE (2020) Sulforaphane bioavailability and chemopreventive activity in men presenting for biopsy of the prostate gland: a randomized controlled trial. Nutr Cancer 72:74–87

    Article  CAS  PubMed  Google Scholar 

  64. Gupta P, Kim B, Kim SH, Srivastava SK (2014) Molecular targets of isothiocyanates in cancer: recent advances. Mol Nutr Food Res 58:1685–1707

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Lewerenz HJ, Bleyl D, Plass R (1992) Subacute oral toxicity study of benzyl isothiocyanate in rats. Food Nahrung 36:190–198

    Article  CAS  PubMed  Google Scholar 

  66. Imaizumi K, Sato S, Sakakibara Y, Mori S, Ohkuma M, Kawashima Y, Ban T, Sasaki H, Tachiyashiki K (2010) Allyl isothiocyanate-induced changes in the distribution of white blood cells in rats. J Toxicol Sci 35:583–589

    Article  CAS  PubMed  Google Scholar 

  67. Kołodziejski D, Piekarska A, Hanschen FS, Pilipczuk T, Tietz F, Kusznierewicz B, Bartoszek A (2019) Relationship between conversion rate of glucosinolates to isothiocyanates/indoles and genotoxicity of individual parts of Brassica vegetables. Eur Food Res Technol 245:383–400

    Article  Google Scholar 

Download references

Funding

Not applicable.

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, Nootan Pharmacy College, Sankalchand Patel University, Visnagar, 384315, Gujarat, India

    Prashant Bhagwan Patil & Jayvadan Kantilal Patel

  2. Department of Pharmaceutical Chemistry, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur, 425405, MH, India

    Prashant Bhagwan Patil

  3. Formulation Scientist, Aavis Pharmaceuticals, Hoschton, 30548, Georgia, United States

    Jayvadan Kantilal Patel

Authors
  1. Prashant Bhagwan Patil
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jayvadan Kantilal Patel
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

PBP wrote the main manuscript text with figures and JKP reviewed and finalize the manuscript.

Corresponding author

Correspondence to Prashant Bhagwan Patil.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

I, the undersigned, give my consent for the publication.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patil, P.B., Patel, J.K. Chemopreventive aspects, investigational anticancer applications and current perspectives on allyl isothiocyanate (AITC): a review. Mol Cell Biochem 478, 2763–2777 (2023). https://doi.org/10.1007/s11010-023-04697-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-023-04697-0

Keywords

Search

Navigation