Abstract
Cancer growth is a molecular mechanism initiated by genetic and epigenetic modifications that are involved in cell proliferation, differentiation, apoptosis, and senescence pathways. Chemoprevention is an important strategy for cancer treatment that leads to blocking, reversing, or impeding the multistep process of tumorigenesis, including the blockage of its vital morphogenetic milestones viz. normal, preneoplasia, neoplasia, and metastasis. Naturally occurring phytochemicals are becoming ever more popular compared to synthetic drugs for many reasons, including safety, bioavailability, efficacy, and easy availability. Allyl isothiocyanate (AITC) is a natural compound present in all plants of the Cruciferae family, such as Brussels sprouts, cauliflower, mustard, cabbage, kale, horseradish, and wasabi. In vitro and in vivo studies carried out over the decades have revealed that AITC inhibits tumorigenesis without any toxicity and undesirable side effects. The bioavailability of AITC is exceedingly high, as it was reported that nearly 90% of orally administered AITC is absorbed. AITC exhibits multiple pharmacological properties among which its anticancer activity is the most significant for cancer treatment. Its anticancer activity is exerted via selective modulation of multiple cell signaling pathways related to oxidative stress, inflammation, cell proliferation, cell cycle arrest, apoptosis, angiogenesis, invasion, and metastasis. This review highlights the current knowledge on molecular targets that are involved in the anticancer effect of AITC associated with (i) inhibition of carcinogenic activation and induction of antioxidants, (ii) suppression of pro-inflammatory and cell proliferative signals, (iii) induction of cell cycle arrest and apoptosis, and (iv) inhibition of angiogenic and invasive signals related to metastasis.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Acknowledgements
We gratefully acknowledge the financial assistance from the Indian Council of Medical Research (ICMR), in the form of a Senior Research Fellowship (SRF), New Delhi, India to the first author Mr. T. Rajakumar.
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This study was funded by the Indian Council of Medical Research (ICMR), Government of India (Grant No. 3/2/2/189/2013/NCD-III (OPA-27129)).
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All authors contributed to the study’s conception and design. Material preparation, data collection, and analysis were performed by TR and PP. The first draft of the manuscript was written by TR and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Rajakumar, T., Pugalendhi, P. Allyl isothiocyanate regulates oxidative stress, inflammation, cell proliferation, cell cycle arrest, apoptosis, angiogenesis, invasion and metastasis via interaction with multiple cell signaling pathways. Histochem Cell Biol 161, 211–221 (2024). https://doi.org/10.1007/s00418-023-02255-9
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DOI: https://doi.org/10.1007/s00418-023-02255-9