Evaluation of the Effects of the Flavonoid Apigenin on Apoptotic Pathway Gene Expression on the Colon Cancer Cell Line (HT29)

Turktekin M., Konaç E., Önen H. İ., Alp E., Yilmaz A., Menevse S.

JOURNAL OF MEDICINAL FOOD, cilt.14, sa.10, ss.1107-1117, 2011 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 10
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1089/jmf.2010.0208
  • Dergi Adı: JOURNAL OF MEDICINAL FOOD
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1107-1117
  • Anahtar Kelimeler: apigenin, apoptosis, caspase-3, caspase-8, colon cancer, cyclin D1, 5-fluorouracil, HT29 cell line, mammalian target of rapamycin, HUMAN PROSTATE-CANCER, FACTOR-KAPPA-B, CYCLE ARREST, HUMAN BREAST, IN-VITRO, GROWTH-INHIBITION, CARCINOMA-CELLS, DIETARY FLAVONOIDS, MDA-MB-453 CELLS, INDUCE APOPTOSIS
  • Gazi Üniversitesi Adresli: Evet

Özet

Apigenin (4',5,7-trihydroxyflavone) is one of the leading components supporting targeted treatment options. We explored the cytotoxic and apoptotic effects of various doses of apigenin administered alone and together with 5-fluorouracil (5-FU)-a chemotherapeutic agent with high cytotoxicity-for different incubation periods, on morphologic, DNA, RNA (messenger RNA [mRNA]), and protein levels on the p53 mutant HT29 human colon adenocarcinoma cell line. Treatment with apigenin alone for a 72-hour incubation at 90-mu M dose resulted in an apoptotic percentage of 24.92% (P=.001). A higher percentage (29.13%) was observed after treatment with the same dose of apigenin plus 5-FU for the same incubation period (P=.001). These results were confirmed as mRNA and protein expression levels of caspase-3 increased 2.567-fold and mRNA expression levels of caspase-8 increased 3.689-fold compared with the control group. On the other hand, mRNA expression levels of mammalian target of rapamycin (mTOR) and cyclin D1 (CCND1) decreased by 0.423-fold and 0.231-fold, respectively. To our knowledge this is the first study showing that treatment with apigenin alone results in cell cycle arrest through activation of caspase cascade and stimulation of apoptosis in HT29 cells. It also shows that use of apigenin plus 5-FU further increases this effect. This study draws attention to the probable clinical effectiveness of apigenin plus a chemotherapeutic agent with high cytotoxicity. It also highlights the induction of desirable apoptotic effects by targeting the caspase cascade pathway through administration of reduced doses for shorter incubation periods.