Department of Physiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Anticancer Agents Med Chem. 2019;19(12):1535-1542. doi: 10.2174/1871520619666190704102708.
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).
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.
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.
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.
结直肠癌(CRC)中甲状腺激素(THs)系统的失调表明这些激素可能在 CRC 的发病机制中发挥作用。类黄酮是多酚化合物,具有很强的抗肿瘤活性,尽管其中一些类黄酮会干扰 THs 生理学的各个方面。类黄酮的抗肿瘤作用是否受 THs 影响尚不清楚。因此,我们研究了在存在和不存在 L-甲状腺素(T4)的情况下,一种众所周知的黄酮类化合物芹菜素(Api)对 SW480 CRC 细胞某些致瘤特性的影响。
通过 MTT 测定法评估细胞活力。使用流式细胞术和 DNA 电泳评估细胞死亡。通过原位检测β-半乳糖苷酶活性来检测细胞衰老。通过抗体阵列技术评估蛋白表达。
虽然 T4 的作用很小,但 Api 通过诱导细胞凋亡减少细胞生长和衰老。Api 和 T4 对凋亡蛋白和促凋亡蛋白的表达有不同的影响。Survivin、HSP60 和 HTRA 是细胞表达最多的蛋白。几乎所有由 Api 诱导的作用在 T4 存在的情况下仍然存在。
这些数据表明,Api 可能通过诱导细胞凋亡而不是细胞坏死或衰老来抑制 CRC 细胞的生长和进展。此外,它们表明 T4 对 CRC 细胞的生长几乎没有影响,并且不能拮抗 Api 的抗生长作用。无论接受何种治疗,细胞均表达高水平的 survivin、HSP60 和 HTRA,表明这些蛋白可能在 SW480 CRC 细胞永生化中发挥核心作用。