Abstract
Angiogenesis, invasion, and metastasis are the main events of cancer cells. JAK-1/STAT-3 is a key intracellular signaling transduction pathway, which controls the growth, differentiation, apoptosis, invasion, and angiogenesis of various cancer cells. The present study explored the impact of allyl isothiocyanate (AITC) on the JAK-1/STAT-3 pathway in DMBA-induced rat mammary tumorigenesis. The mammary tumor was initiated through a single dose of 25 mg DMBA/rat by a subcutaneous injection administered near the mammary gland. We observed decreased body weight and increased the total number of tumors, tumor incidence, tumor volume, well-developed tumor, and histopathological abnormalities in DMBA-induced rats that were modulated after being treated with AITC. Staining of mammary tissues showed a high accumulation of collagen in DMBA-induced rats and it was normalized by the AITC treatment. Moreover, DMBA-induced mammary tissues showed up-regulated expressions of EGFR, pJAK-1, pSTAT-3, nuclear fraction of STAT-3, VEGF, VEGFR2, HIF-1α, MMP-2, and MMP-9 and the down-regulated expressions of cytosolic fraction of STAT-3 and TIMP-2. Oral administration of AITC on DMBA-induced rats inhibits angiogenesis and invasion by modifying these angiogenic and invasive markers. The finding of the present study was further confirmed by molecular docking analysis that shows a strong binding interaction between AITC with STAT-3 and cocrystal structure of STAT-3 glide energy of −18.123 and −72.246 (kcal/mole), respectively. Overall, the results suggested that AITC inhibits activation of the JAK-1/STAT-3 pathway, which subsequently prevents angiogenesis and invasion. It was recommended that AITC might develop a beneficial effect against breast cancer.
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Data availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- JAK:
-
Janus kinase
- STAT:
-
Signal transducer and activator of transcription
- EGF:
-
Epidermal growth factor
- EGFR:
-
Epidermal growth factor receptor
- AITC:
-
Allyl isothiocyanate
- H&E:
-
Hematoxylin and eosin
- MT:
-
Masson's tri-chrome
- PR:
-
Picrosirius red
- RT:
-
Reverse transcription
- PCR:
-
Polymerase chain reaction
- EtBr:
-
Ethidium bromide
- ECM:
-
Extracellular matrix
- BM:
-
Basement membrane
- ROS:
-
Reactive oxygen species
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Acknowledgements
We gratefully acknowledged the financial assistance from the Indian Council of Medical Research (ICMR, Grant number-3/2/2/189/2013/NCD-III (OPA-27129)), in the form of a Senior Research Fellowship (SRF), New Delhi, India to the first author, Mr. T. Rajakumar.
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The authors declare that all data were generated in-house and that no paper mill was used. All authors contributed to the study's conception and design. Material preparation, data collection, and analysis were performed by [Thangarasu Rajakumar] and [Pachaiappan Pugalendhi]. The first draft of the manuscript was written by [Thangarasu Rajakumar] 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 inhibits invasion and angiogenesis in breast cancer via EGFR-mediated JAK-1/STAT-3 signaling pathway. Amino Acids 55, 981–992 (2023). https://doi.org/10.1007/s00726-023-03285-2
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DOI: https://doi.org/10.1007/s00726-023-03285-2