In the bioethanol production process employing citrus peels, a large amount of enzymatic hydrolyzed residues is generated as waste material. The bioactive compounds, and antioxidant and anticancer activities of these residues were investigated in the present study. Hydrolyzed citrus residues exhibited similar antioxidant activity as the unhydrolyzed control, which was positively correlated to the contents of total phenols, flavonoids and total carotenoid. Some flavonoids (naringin, naringenin, hesperetin and neohesperidin) and two high value co-products (D-limonene and galacturonic acid) were detected only in hydrolyzed residues. In addition, hydrolyzed residues showed antiproliferative activity and sub-G1 arrest in human melanoma A375 and colon cancer HCT116 cells. These results provide an alternative use for hydrolyzed citrus residues in the functional food, cosmetic and pharmaceutical industries.

A Satsuma mandarin (Citrus unshiu Marc. cv. Miyagawa) spontaneous mutant, Shinheungri, produces fruit with an abnormal red-coloured peel during ripening. The peel and pulp extracts of Shinheungri fruit were evaluated for polyphenolic contents and antioxidant activities by using various in vitro assays. Compared with those of wild type (WT), Shinheungri exhibited slightly higher total flavonoid content and antioxidant activities. The results of UPLC analyses indicate that the peel and pulp extracts of Shinheungri fruit were rich in mainly hesperidin, and they had different flavonoid composition. The present data on Shinheungri revealed a potential source of powerful flavonoids for further detailed phytochemical investigation.

Doxorubicin is a general chemotherapy drug widely used for a number of cancers. However, the correlation between endogenous nitric oxide (NO • ) levels and chemoresistance to doxorubicin remains unclear. In this study, we investigated the effect of endogenous NO• on the anticancer activity of doxorubicin in human colon cancer cell lines HCT116 and HT29 with different p53 status. The cells were treated with either doxorubicin alone or in combination with the NO• synthase (NOS) inhibitor N G -monomethyl-L-arginine (NMA). Doxorubicin differentially inhibited the growth of both the HCT116 (p53-WT) and HT29 (p53-MUT) cells, which was mitigated by cotreatment with NMA. Further studies revealed that inhibition of endogenous NO• mitigated doxorubicin-induced apoptosis in the HCT116 and HT29 cells, as evidenced by apoptotic DNA fragmentation and the sub-G1 peak of apoptotic markers. Apoptosis was delayed in the HT29 cells, and its magnitude was greatly reduced, underscoring the importance of the modulation of p53 in the response. RT-PCR analysis revealed that doxorubicin down-regulated levels of inhibitors of the apoptosis family (cellular IAP-1 and -2). Collectively, these data show that induction of apoptosis by doxorubicin in human colon cancer cells is possibly related to modulation of endogenous NO• , the expression of the IAP family of genes, and the status of p53. The underlying mechanisms may represent potential targets for adjuvant strategies to improve the efficacy of chemotherapy for colon cancer.