Introduction: Deregulation of Thyroid Hormones (THs) system in Colorectal Cancer (CRC) suggests
that these hormones may play roles in CRC pathogenesis. Flavonoids are polyphenolic compounds, which possess
potent antitumor activities and interfere, albeit some of them, with all aspects of THs physiology. Whether
the antitumor actions of flavonoids are affected by THs is unknown. Therefore, we investigated the effects of
apigenin (Api), a well-known flavone, on some tumorigenic properties of SW480 CRC cells in the presence and
absence of L-thyroxine (T4).
Methods: Cell viability was assessed by MTT assay. Flow cytometry and DNA electrophoresis were used to
evaluate cell death. Cell senescence was examined by in situ detection of β-galactosidase activity. Protein expression
was assessed by antibody array technique.
Results: While T4 had minimal effects, Api reduced cell growth and senescence by induction of apoptosis.
Expression of anti-apoptotic and pro-apoptotic proteins were differentially affected by Api and T4. Survivin,
HSP60 and HTRA were the most expressed proteins by the cells. Almost all Api-induced effects persisted in the
presence of T4.
Conclusion: These data suggest that Api may inhibit CRC cell growth and progression through induction of
apoptosis rather than cell necrosis or senescence. In addition, they suggest that T4 has minimal effects on CRC
cell growth, and is not able to antagonize the anti-growth effects of Api. Regardless of the treatments, cells
expressed high levels of survivin, HSP60 and HTRA, indicating that these proteins may play central roles in
SW480 CRC cell immortality.