Authors : Ahana Sinha; Gouri Karan; Subhabrata Das; Tanmoy Maity; Dr. Sujata Maiti Choudhury

Volume/Issue : Volume 10 - 2025, Issue 7 - July

Google Scholar : https://tinyurl.com/2s35ce4s

Scribd : https://tinyurl.com/yzv2shb8

DOI : https://doi.org/10.38124/ijisrt/25jul270

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Abstract : Cancer remains a pressing global health issue, with its burden intensified by factors such as increased life expectancy, urbanization, and shifts in environmental and lifestyle patterns. Defined by unregulated cell growth, invasive behavior, and the ability to metastasize, cancer continues to be a principal cause of death and disease globally. In response, there has been growing interest in natural phytochemicals as adjuncts or alternatives to traditional cancer therapies, largely due to their broad-spectrum biological activities and relatively lower toxicity. Benzyl isothiocyanate (BITC), a naturally occurring compound released from glucosinolates in cruciferous vegetables and papaya seeds via myrosinase action, has emerged as a potential anticancer agent. A wealth of preclinical evidence supports BITC's efficacy in cancer prevention and treatment, attributing its effects to mechanisms such as apoptosis induction, disruption of cell cycle progression, suppression of metastasis, and regulation of oncogenic signaling cascades. Recent advancements in nanotechnology have further enhanced BITC's therapeutic potential by improving its stability, bioavailability, and selective toxicity toward malignant cells while sparing normal tissues.

Keywords : Phytochemical, Benzyl Isothiocyanate, Nano-Formulation, Anti-Neoplastic Effect, Cancer Cell.

References :

1. Abe N, Hou DX, Munemasa S, Murata Y, Nakamura Y. Nuclear factor-kappaB sensitizes to benzyl isothiocyanate-induced antiproliferation in p53-deficient colorectal cancer cells. Cell Death & Disease. 2014 Nov;5(11):e1534-.
2. Ali SS, Ahmad N, Jamal Gilani S, Ali Khan N. Isothiocyanates: a review. Research Journal of Pharmacognosy. 2018 Apr 1;5(2):71-89.
3. Anand P, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB. Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical research. 2008 Sep;25(9):2097-116.
4. Anand U, Dey A, Chandel AK, Sanyal R, Mishra A, Pandey DK, De Falco V, Upadhyay A, Kandimalla R, Chaudhary A, Dhanjal JK. Cancer chemotherapy and beyond: Current status, drug candidates, associated risks and progress in targeted therapeutics. Genes & diseases. 2023 Jul 1;10(4):1367-401.
5. Avato P, Argentieri MP. Brassicaceae: A rich source of health improving phytochemicals. Phytochemistry reviews. 2015 Dec;14(6):1019-33.
6. Basilotta R. In vitro and In vivo evaluation of signaling pathways underlying the tumor suppressive effect of benzyl isothiocyanate in anaplastic thyroid carcinoma.
7. Basu A, Haldar S. Anti-proliferative and proapoptotic effects of benzyl isothiocyanate on human pancreatic cancer cells is linked to death receptor activation and RasGAP/Rac1 down-modulation. International journal of oncology. 2009 Sep 1;35(3):593-9.
8. Batra S, Sahu RP, Kandala PK, Srivastava SK. Benzyl isothiocyanate–mediated inhibition of histone deacetylase leads to NF-κB turnoff in human pancreatic carcinoma cells. Molecular cancer therapeutics. 2010 Jun 1;9(6):1596-608.

9. Batra S, Sahu RP, Kandala PK, Srivastava SK. Benzyl isothiocyanate–mediated inhibition of histone deacetylase leads to NF-κB turnoff in human pancreatic carcinoma cells. Molecular cancer therapeutics. 2010 Jun 1;9(6):1596-608.
10. Batra S, Sahu RP, Kandala PK, Srivastava SK. Benzyl isothiocyanate–mediated inhibition of histone deacetylaseleads to NF-κB turnoff in human pancreatic carcinoma cells. Molecular cancer therapeutics. 2010 Jun 1;9(6):1596-608.
11. Behl T, Rocchetti G, Chadha S, Zengin G, Bungau S, Kumar A, Mehta V, Uddin MS, Khullar G, Setia D, Arora S. Phytochemicals from plant foods as potential source of antiviral agents: An overview. Pharmaceuticals. 2021 Apr 19;14(4):381.
12. Bhat AS, Ahmed M, Abbas K, Mustafa M, Alam M, Salem MA, Islam S, Tantry IQ, Singh Y, Fatima M, Usmani N. Cancer initiation and progression: a comprehensive review of carcinogenic substances, anti-cancer therapies, and regulatory frameworks. Asian J. Res. Biochem.. 2024;14(4):111-25.
13. Boreddy SR, Pramanik KC, Srivastava SK. Pancreatic tumor suppression by benzyl isothiocyanate is associated with inhibition of PI3K/AKT/FOXO pathway. Clinical Cancer Research. 2011 Apr 1;17(7):1784-95.
14. Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008–2030): a population-based study. The lancet oncology. 2012 Aug 1;13(8):790-801.
15. Cai K, Jiang L, Wang J, Zhang H, Wang X, Cheng D, Dou J. Downregulation of β-catenin decreases the tumorigenicity, but promotes epithelial-mesenchymal transition in breast cancer cells. Journal of cancer research and therapeutics. 2014 Oct 1;10(4):1063-70.
16. Chavda VP, Patel AB, Mistry KJ, Suthar SF, Wu ZX, Chen ZS, Hou K. Nano-drug delivery systems entrapping natural bioactive compounds for cancer: recent progress and future challenges. Frontiers in oncology. 2022 Mar 29;12:867655.
17. Chen CY, Kao CL, Liu CM. The cancer prevention, anti-inflammatory and anti-oxidation of bioactive phytochemicals targeting the TLR4 signaling pathway. International journal of molecular sciences. 2018 Sep 12;19(9):2729.
18. Choudhari AS, Mandave PC, Deshpande M, Ranjekar P, Prakash O. Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Frontiers in pharmacology. 2020 Jan 28;10:1614.
19. Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, Kitui SK, Manyazewal T. New approaches and procedures for cancer treatment: Current perspectives. SAGE open medicine. 2021 Aug;9:20503121211034366.
20. Dwivedi S, Kushalan S, Paithankar JG, D’Souza LC, Hegde S, Sharma A. Environmental toxicants, oxidative stress and health adversities: Interventions of phytochemicals. Journal of pharmacy and pharmacology. 2022 Apr 1;74(4):516-36.

21. Getahun SM, Chung FL. Conversion of glucosinolates to isothiocyanates in humans after ingestion of cooked watercress. Cancer Epidemiology Biomarkers & Prevention. 1999 May 1;8(5):447-51.
22. Gonzalvez F, Ashkenazi A. New insights into apoptosis signaling by Apo2L/TRAIL.Oncogene. 2010 Aug;29(34):4752-65.
23. Guo S, Liu M, Gonzalez-Perez RR. Role of Notch and its oncogenic signaling crosstalk in breast cancer. Biochimicaet Biophysica Acta (BBA)-Reviews on Cancer. 2011 Apr 1;1815(2):197-213.
24. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. cell. 2011 Mar 4;144(5):646-74.
25. Hinchman CA, Ballatori N. Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process. Journal of Toxicology and Environmental Health, Part A Current Issues. 1994 Apr 1;41(4):387-409.
26. Hwang ES, Lee HJ. Benzyl isothiocyanate inhibits metalloproteinase-2/-9 expression by suppressing the mitogen-activated protein kinase in SK-Hep1 human hepatoma cells. Food and chemical toxicology. 2008 Jul 1;46(7):2358-64
27. Hwang ES, Lee HJ. Benzyl isothiocyanate inhibits metalloproteinase-2/-9 expression by suppressing the mitogen-activated protein kinase in SK-Hep1 human hepatoma cells. Food and chemical toxicology. 2008 Jul 1;46(7):2358-64.
28. Idrees H, Zaidi SZ, Sabir A, Khan RU, Zhang X, Hassan SU. A review of biodegradable natural polymer-based nanoparticles for drug delivery applications.Nanomaterials. 2020 Oct 5;10(10):1970.
29. Kadir NH, Rahaman MH, Shahinuzzaman M, Yaakob Z, Alam M. Benzyl Isothiocyanate (BITC) instigated selective cytotoxicity effects on breast cancer cell line, MCF‐7 cells and human Normal fibroblast cells, CRL‐2522 and its bioavailability in Miswak (Salvadora persica L.): In vitro and in silico perspective. Biointerface Research in Applied Chemistry. 2023;13:1-6.
30. Kaufman RJ, Malhotra JD. Calcium trafficking integrates endoplasmic reticulum function with mitochondrial bioenergetics. BiochimicaetBiophysicaActa (BBA)-Molecular Cell Research. 2014 Oct 1;1843(10):2233-9.
31. Khan I, Ali JS, Ul-Haq I, Zia M. Biological and phytochemicals properties of Monothecabuxifolia: an unexplored medicinal plant. Pharmaceutical Chemistry Journal. 2020 Jun;54:293-301.
32. Kim EJ, Eom SJ, Hong JE, Lee JY, Choi MS, Park JH. Benzyl isothiocyanate inhibits basal and hepatocyte growth factor-stimulated migration of breast cancer cells. Molecular and cellular biochemistry. 2012 Jan;359:431-40.
33. Kim SH, Sehrawat A, Singh SV. Notch2 activation by benzyl isothiocyanate impedes its inhibitory effect on breast cancer cell migration. Breast cancer research and treatment. 2012 Aug;134:1067-79.

34. Lai KC, Huang AC, Hsu SC, Kuo CL, Yang JS, Wu SH, Chung JG. Benzyl isothiocyanate (BITC) inhibits migration and invasion of human colon cancer HT29 cells by inhibiting matrix metalloproteinase-2/-9 and urokinase plasminogen (uPA) through PKC and MAPK signaling pathway. Journal of agricultural and food chemistry. 2010 Mar 10;58(5):2935-42.
35. Lecarpentier Y, Schussler O, Hébert JL, Vallée A. Multiple targets of the canonical WNT/β-catenin signaling in cancers. Frontiers in oncology. 2019 Nov 18;9:1248.
36. Lee CF, Chiang NN, Lu YH, Huang YS, Yang JS, Tsai SC, Lu CC, Chen FA. Benzyl isothiocyanate (BITC) triggers mitochondria-mediated apoptotic machinery in human cisplatin-resistant oral cancer CAR cells. Biomedicine. 2018 Sep;8(3).
37. Lee JH, Khor TO, Shu L, Su ZY, Fuentes F, Kong AN. Dietary phytochemicals and cancer prevention: Nrf2 signaling, epigenetics, and cell death mechanisms in blocking cancer initiation and progression. Pharmacology & therapeutics. 2013 Feb 1;137(2):153-71.
38. Lin JF, Tsai TF, Liao PC, Lin YH, Lin YC, Chen HE, Chou KY, Hwang TI. Benzyl isothiocyanate induces protective autophagy in human prostate cancer cells via inhibition of mTORsignaling. Carcinogenesis. 2013 Feb 1;34(2):406-14.
39. Lin JF, Tsai TF, Yang SC, Lin YC, Chen HE, Chou KY, Thomas I, Hwang S. Benzyl isothiocyanate induces reactive oxygen species-initiated autophagy and apoptosis in human prostate cancer cells. Oncotarget. 2017 Mar 3;8(12):20220.
40. Liu KC, Huang YT, Wu PP, Ji BC, Yang JS, Yang JL, Chiu TH, Chueh FS, Chung JG.The roles of AIF and Endo G in the apoptotic effects of benzyl isothiocyanate on DU 145 human prostate cancer cells via the mitochondrial signaling pathway. International journal of oncology. 2011 Mar 1;38(3):787-96.
41. Liu Y, Zhang L, Meng Y, Huang L. Benzyl isothiocyanate inhibits breast cancer cell tumorigenesis via repression of the FoxH1-Mediated Wnt/β-catenin pathway. International Journal of Clinical and Experimental Medicine. 2015;8(10):17601.
42. Lui VW, Wentzel AL, Xiao D, Lew KL, Singh SV, Grandis JR. Requirement of a carbon spacer in benzyl isothiocyanate-mediated cytotoxicity and MAPK activation in head and neck squamous cell carcinoma. Carcinogenesis. 2003 Oct 1;24(10):1705-12.
43. Mi L, Di Pasqua AJ, Chung FL. Proteins as binding targets of isothiocyanates in cancer prevention. Carcinogenesis. 2011 Oct 1;32(10):1405-13.
44. Minarini A, Milelli A, Fimognari C, Simoni E, Turrini E, Tumiatti V. Exploring the effects of isothiocyanates on chemotherapeutic drugs. Expert Opinion on Drug Metabolism & Toxicology. 2014 Jan 1;10(1):25-38.

45. Miyoshi N, Uchida K, Osawa T, Nakamura Y. A link between benzyl isothiocyanate-induced cell cycle arrest and apoptosis: involvement of mitogen-activated protein kinases in the Bcl-2 phosphorylation. Cancer Research. 2004 Mar 15;64(6):2134-42.
46. Mottola M, Bertolino MC, Kourdova LT, Valdivia Pérez JA, Bogino MF, Nocelli NE, Chaveriat L, Martin P, Vico RV, Fabro G, Fanani ML. Nanoemulsions of synthetic rhamnolipids act as plant resistance inducers without damaging plant tissues or affecting soil microbiota. Frontiers in Plant Science. 2023 Aug 22;14:1195718.
47. Petropoulos S, Di Gioia F, Ntatsi G. Vegetable organosulfur compounds and their health promoting effects. Current pharmaceutical design. 2017 May 1;23(19):2850-75.
48. Pratheeshkumar P, Sreekala C, Zhang Z, Budhraja A, Ding S, Son YO, Wang X, Hitron A, Hyun-Jung K, Wang L, Lee JC. Cancer prevention with promising natural products: mechanisms of action and molecular targets. Anti-Cancer Agents in Medicinal Chemistry-Anti-Cancer Agents). 2012 Dec 1;12(10):1159-84.
49. Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy.Frontiers in oncology. 2022 Oct 12;12:985363.
50. Rahman R, Al-Sabahi JN, Ghaffar A, Nadeem F, Umar A. Phytochemical, morphological, botanical, and pharmacological aspects of a medicinal plant: Kalanchoe pinnata–A review article. International Journal of Chemical and Biochemical Sciences. 2019 Oct;16:5-10.
51. Ribatti D, Tamma R, Annese T. Epithelial-mesenchymal transition in cancer: a historical overview. Translational oncology. 2020 Jun 1;13(6):100773.
52. Rudzińska A, Juchaniuk P, Oberda J, Wiśniewska J, Wojdan W, Szklener K, Mańdziuk S. Phytochemicals in cancer treatment and cancer prevention—review on epidemiological data and clinical trials. Nutrients. 2023 Apr 14;15(8):1896.
53. Sadikovic B, Al-Romaih K, Squire JA, Zielenska M. Cause and consequences of genetic and epigenetic alterations in human cancer. Current genomics. 2008 Sep 1;9(6):394-408.
54. Sahu RP, Srivastava SK. The role of STAT-3 in the induction of apoptosis in pancreatic cancer cells by benzyl isothiocyanate. Journal of the National Cancer Institute. 2009 Feb 4;101(3):176-93
55. Saini A, Kumar M, Bhatt S, Saini V, Malik A. Cancer causes and treatments. Int J Pharm Sci Res. 2020 Jul;11(7):3121-34.
56. Sehrawat A, Singh SV. Benzyl isothiocyanate inhibits epithelial-mesenchymal transition in cultured and xenografted human breast cancer cells. Cancer Prevention Research. 2011 Jul 1;4(7):1107-17.

57. Selvaraj S, Sun Y, Sukumaran P, Singh BB. Resveratrol activates autophagic cell death in prostate cancer cells via downregulation of STIM1 and the mTOR pathway. Molecular carcinogenesis. 2016 May;55(5):818-31.
58. Shahidi F, Hossain A. Role of lipids in food flavor generation. Molecules. 2022 Aug 6;27(15):5014.
59. Sharif HR, Goff HD, Majeed H, Liu F, Nsor-Atindana J, Haider J, Liang R, Zhong F. Physicochemical stability of β-carotene and α-tocopherol enriched nanoemulsions: Influence of carrier oil, emulsifier and antioxidant. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2017 Sep 20;529:550-9.
60. Shim MS, Liton PB. The physiological and pathophysiological roles of the autophagy lysosomal system in the conventional aqueous humor outflow pathway: More than cellular clean up. Progress in retinal and eye research. 2022 Sep 1;90:101064.
61. Singh VK, Arora D, Ansari MI, Sharma PK. Phytochemicals based chemopreventive and chemotherapeutic strategies and modern technologies to overcome limitations for better clinical applications. Phytotherapy Research. 2019 Dec;33(12):3064-89.
62. Singh, A. V., Xiao, D., Lew, K. L., Dhir, R., & Singh, S. V. Benzyl isothiocyanate inhibits growth of human prostate cancer xenografts in vivo via apoptosis induction. Clinical Cancer Research, 2009, 10(22), 7709–7716.
63. Szczyglewska P, Feliczak-Guzik A, Nowak I. Nanotechnology–general aspects: A chemical reduction approach to the synthesis of nanoparticles. Molecules. 2023 Jun 22;28(13):4932.
64. Thakur M, Singh K, Khedkar R. Phytochemicals: Extraction process, safety assessment, toxicological evaluations, and regulatory issues. InFunctional and preservative properties of phytochemicals 2020 Jan 1 (pp. 341-361).Academic Press.
65. Tian T, Tong X, Yuan Y, Lyu B, Jiang D, Cui W, Cheng X, Li L, Li Y, Jiang L, Wang H. Preparation of benzyl isothiocyanatenanoemulsions by different emulsifiers: Stability and bioavailability. Process Biochemistry. 2021 Dec 1;111:128-38.
66. Trudel M, Mulligan L, Cavenee W, Margolese R, Côté J, Gariépy G. Retinoblastoma and p53 gene product expression in breast carcinoma: immunohistochemical analysis and clinicopathologic correlation. Human pathology. 1992 Dec 1;23(12):1388-94.
67. Tsai TF, Chen PC, Lin YC, Chou KY, Chen HE, Ho CY, Lin JF, Hwang TI. Benzyl isothiocyanate promotes miR‐99a expression through ERK/AP‐1‐dependent pathway in bladder cancer cells. Environmental toxicology. 2020 Jan;35(1):47-54.
68. Uppal S, Kaur K, Kumar R, Kaur ND, Shukla G, Mehta SK. Chitosan nanoparticles as a biocompatible and efficient nanowagon for benzyl isothiocyanate. International journal of biological macromolecules. 2018 Aug 1;115:18-28.

69. Uppal S, Kumar R, Sareen S, Kaur K, Mehta SK. Biofabrication of cerium oxide nanoparticles using emulsification for an efficient delivery of Benzyl isothiocyanate. Applied Surface Science. 2020 Apr 30;510:145011.
70. Valencia M, Kim SR, Jang Y, Lee SH. Neuronal autophagy: characteristic features and roles in neuronal pathophysiology. Biomolecules & Therapeutics. 2021 Apr 20;29(6):605.
71. Wang H, OoKhor T, Shu L, Su ZY, Fuentes F, Lee JH, Tony Kong AN. Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Cancer Agents). 2012 Dec 1;12(10):1281-305.
72. Wang X, Zhou Y, Tan R, Xiong M, He W, Fang L, Wen P, Jiang L, Yang J. Mice lacking the matrix metalloproteinase-9 gene reduce renal interstitial fibrosis in obstructive nephropathy. American Journal of Physiology-Renal Physiology. 2010 Nov;299(5):F973-82.
73. Warin R, Xiao D, Arlotti JA, Bommareddy A, Singh SV. Inhibition of human breast cancer xenograft growth by cruciferous vegetable constituent benzyl isothiocyanate. Molecular Carcinogenesis: Published in cooperation with the University of Texas MD Anderson Cancer Center. 2010 May;49(5):500-7.
74. Xiao D, Bommareddy A, Kim SH, Sehrawat A, Hahm ER, Singh SV. Benzyl isothiocyanate causes FoxO1-mediated autophagic death in human breast cancer cells. PloS one. 2012 Mar 22;7(3):e32597.
75. Xiao, D., Powolny, A. A., & Singh, S. V. Benzyl isothiocyanate causes mitotic arrest and induces apoptosis in human prostate cancer cells. Molecular Cancer Therapeutics, 2014; 4(9), 1373–1380.
76. Xie B, Nagalingam A, Kuppusamy P, Muniraj N, Langford P, Győrffy B, Saxena NK, Sharma D. Benzyl Isothiocyanate potentiates p53 signaling and antitumor effects against breast cancer through activation of p53-LKB1 and p73-LKB1 axes. Scientific reports. 2017 Jan 10;7(1):40070.
77. Yeh YT, Hsu YN, Huang SY, Lin JS, Chen ZF, Chow NH, Su SH, Shyu HW, Lin CC, Huang WT, Yeh H. Benzyl isothiocyanate promotes apoptosis of oral cancer cells via an acute redox stress-mediated DNA damage response. Food and Chemical Toxicology. 2016 Nov 1;97:336-45.
78. Zakaria S, Helmy MW, Salahuddin A, Omran G. Chemopreventive and antitumor effects of benzyl isothiocynate on HCC models: A possible role of HGF/pAkt/STAT3 axis and VEGF. Biomedicine & Pharmacotherapy. 2018 Dec 1;108:65-75.
79. Zhang QC, Pan ZH, Liu BN, Meng ZW, Wu X, Zhou QH, Xu K. Benzyl isothiocyanate induces protective autophagy in human lung cancer cells through an endoplasmic reticulum stress-mediated mechanism. ActaPharmacologicaSinica. 2017 Apr;38(4):539-50.

80. Zhang R, Loganathan S, Humphreys I, Srivastava SK. Benzyl isothiocyanate-induced DNA damage causes G2/M cell cycle arrest and apoptosis in human pancreatic cancer cells. The Journal of nutrition. 2006 Nov 1;136(11):2728-34.
81. Zhu M, Li W, Dong X, Chen Y, Lu Y, Lin B, Guo J, Li M. Benzyl-isothiocyanate induces apoptosis and inhibits migration and invasion of hepatocellular carcinoma cells in vitro. Journal of Cancer. 2017;8(2):240.