Hepatocellular carcinoma is a lethal cancer with high recurrence ratio and lacks effective therapeutics. In the past few years, it has been reported that increased intake of vegetables and fruits could reduce the cancer incidence, which suggests dietary agents might possess anticancer effects. Eriocitrin is a flavonoid isolated from lemon, which is known as a strong antioxidant agent. We here for the first time demonstrated that eriocitrin could inhibit the proliferation of hepatocellular carcinoma cell lines by arresting cell cycle in S phase through up-regulation of p53, cyclin A, cyclin D3 and CDK6. Furthermore, we found that eriocitrin could trigger apoptosis by activating mitochondria-involved intrinsic signaling pathway. Thus, eriocitrin might be regarded as a potential chemopreventive natural product to inhibit the early malignant transformation of hepatocellular carcinoma.
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This work was supported by National Natural Science Foundation of China (31170676, 81300398), Natural Science Foundation of Guangdong Province, China (2015A030313518), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry (2014-1685) and Scientific Research Foundation for Returned Overseas Scholars of Guangdong Medical College, China (B2012082). This work was also supported by the funds from 2013 Sail Plan “the introduction of the Shortage of Top-Notch Talent” Project (YueRenCai-Ban  1), Science and Technology Planning Project (2013B021800072) and Education Discipline Construction Project (2013KJCX0090) of Guangdong Province, China.
Conflict of interest
The authors have declared that there are no conflict of interests to disclose.
Ziyou Wang and Hua Zhang have contributed equally to this work.
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Wang, Z., Zhang, H., Zhou, J. et al. Eriocitrin from lemon suppresses the proliferation of human hepatocellular carcinoma cells through inducing apoptosis and arresting cell cycle. Cancer Chemother Pharmacol 78, 1143–1150 (2016). https://doi.org/10.1007/s00280-016-3171-y
- Hepatocellular carcinoma
- Cell cycle arrest