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Anti‐mitogenic and Chemo‐Sensitizing Activities of Syringic Acid in Human Colorectal Cancer Cells: potential molecular mechanisms of action
Author(s) -
Abaza Mohamed Salah I.,
Afzal Mohamed,
AlAttiyah Rajaa,
Bhardwaj Radhika,
Abbadi Ghanim,
Koyippally Mathew
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.621.2
Bioactivity guided fractionation of methanolic extract of Tamarax aucheriana lead to isolation of its major bioactive material identified as syringic acid by UV, IR, EIMS, CIMS, H1NMR and C13NMR. Anti‐mitogenic and chemosensitizing potentials of syringic acid were studied in human colorectal cancer cells. Syringic acid had a time and dose dependent potent anti‐mitogenic effect on colorectal cancer cells with little effect on normal human fibroblasts. Syringic acid produced time dependent changes in cancer cell cycle distribution. Syringic acid induced apoptosis, moderately inhibited cell invasion, moderately inhibited NFkB activity and markedly inhibited angiogenesis in colorectal cancer cells. Syringic acid downregulated the expression of cyclins B, C, E and H, AIF, cIAP‐1, cIAP‐2, Bcl2 and FLIP. Syringic acid upregulated the expression of Cdk1, CDk2, Cdk7, p19, p21, p27, Bad, Bak, Bax, Bid, Bim, Apaf1, Smac and caspases 2, 3, 6, 7, 8 and 9. Syringic acid differentially sensitized cancer cells to camptothecin, 5FU, oxaloplatin, doxorubicin, taxol, vinblastin, vincristin, etoposide, ellipticine, amsacrine, homoharringtone and aphidicolin. Together, these results clearly indicate the potential of syringic acid as anti‐mitogenic and chemosensitizing agent to human colorectal cancer.