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Nutrients 2019, 11(4), 770; https://doi.org/10.3390/nu11040770

Luteolin Shifts Oxaliplatin-Induced Cell Cycle Arrest at G0/G1 to Apoptosis in HCT116 Human Colorectal Carcinoma Cells

School of Food Science and Biotechnology, Kyungpook National University, Daegu 41566, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 8 March 2019 / Revised: 24 March 2019 / Accepted: 29 March 2019 / Published: 2 April 2019
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Abstract

Certain antioxidative flavonoids are known to activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates cellular antioxidants and detoxifying response and is reportedly highly activated in many types of cancers. Few studies on the potential undesired effects of flavonoid intake during chemotherapy have been conducted, yet Nrf2 activators could favor cancer cell survival by attenuating chemotherapeutic efficiency. This study aimed to examine if luteolin, an Nrf2 activator, hinders chemotherapeutic activity of oxaliplatin, a potent anticancer agent for colorectal cancer, in HCT116 cells. Luteolin treatment strongly increased the transcriptional activity of the antioxidant response element in HCT116 cells and induced the protein expression of heme oxygenase-1, which were indicative of its Nrf2-inducing potential. Intriguingly, 25 μM luteolin reduced cell viability through apoptotic induction, which was intensified in p53-expressing cells while 1 μM oxaliplatin caused cell cycle arrest at G0/G1-phase via the p53/p21-dependent mechanism. Moreover, luteolin treatment was found to reduce oxaliplatin-treated p53-null cell viability and colony counts further, thereby demonstrating an additional effect of luteolin in the killing of human colorectal tumor HCT116 cells not expressing functional p53 protein. The findings suggest that luteolin can induce p53-mediated apoptosis regardless of oxaliplatin treatment and may eliminate oxaliplatin-resistant p53-null colorectal cells. View Full-Text
Keywords: flavonoid; luteolin; oxaliplatin; colorectal cancer; anticancer flavonoid; luteolin; oxaliplatin; colorectal cancer; anticancer
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Jang, C.H.; Moon, N.; Oh, J.; Kim, J.-S. Luteolin Shifts Oxaliplatin-Induced Cell Cycle Arrest at G0/G1 to Apoptosis in HCT116 Human Colorectal Carcinoma Cells. Nutrients 2019, 11, 770.

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