Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 98, Issue -, Pages 523-530Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.12.049
Keywords
Oral cancer; Indole alkaloid; DMBA; EGFR; NF-kappa B; STAT3
Funding
- Indian Council of Medical Research (ICMR), Government of India, New Delhi [45/26/2012/PHA-BMS]
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Gramine, a natural indole alkaloid found in Hordeum vulgare has been possesses anti-mutagenic properties. The aim of the present study was to evaluate the effect of gramine on inflammation and proliferation in 7,12-dimethylbenz[a] anthracene(DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Epidermal growth factor receptor (EGFR) tyrosine kinase phosphorylation trigged PI3K/Akt/mTOR and JAK signaling that activates NF-kappa B and STAT3. In contrast, gramine suppressed EGFR tyrosine kinase phosphorylation and simultaneously inhibiting PI3K/Akt/mTOR and JAK phosphorylation, thereby blockage NF-kappa B and STAT3 nuclear translocation. Attenuation of these oncogenic signals leads to downregulated iNOS, COX-2, TNF-alpha, IL-6, cyclin D1 and PCNA protein expressions. In addition, gramine enhanced the expression of the tumor suppressors p53, p21((WAF1/CIP1)) and Gsk-3 beta by inhibiting MDM2. These results suggested that gramine exhibited anti-inflammation and anti-proliferation effects via suppressed EGFR/PI3K/Akt/mTOR/IKK/NF-kappa B and JAK/STAT3 signaling pathways.
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