EVALUATION OF CELL DEATH MECHANISMS INDUCED BY HYPERICIN AND ITS DERIVATIVE IN COLORECTAL CARCINOMA MODELS

Youssef M. Shehata, Hala M. Ali* and Nermin Raafat

ABSTRACT

Colorectal cancer (CRC) is the third most malignancy and the fourth human killer. Photodynamic therapy (PDT) has emerged as a promising alternative to conventional cancer therapies. This study aimed to investigate the ability of Hypericin (HY) and its derivative (HAHY) as synthetic photosensitizers (PSs) to induce tumoricidal effect in HCT-116 carcinoma models. Sixty balb/c male mice were transplanted with 5×105 HCT-116 cells to induce carcinoma bearing mice model. The experimental animals were then divided into five groups; Group I (untreated), Group II (HY-PDT), Group III (HAHY-PDT), Group IV (HY-PDT+EGCG) and Group V (FOLFOX). Blood, liver and tumor mass samples were taken. Also, biochemical studies and MTT assay were performed. HY and HAHY - PDT had a significant cytotoxic effect on human HCT-116 cells. Also, a significant upregulation in gene expression of P53 and CYT-c in concentration dose dependent manner. Furthermore, a significant increase in IL-6 gene expression in group (2) higher than that in group (3).Whereas it decreased in group (5), and showed insignificant difference in group (4) .Also, results showed decrease in VEGF gene expression in both group (3) and (4), while it showed significant increase in group (2) and slight increase in group (5). In conclusion, these PSs possess a strong cytotoxic and apoptotic effect on human HCT-116 cells. Using of EGCG along with HY-PDT improves the outcome. Also, HAHY-PDT can be used as an alternative to HY-PDT, where it showed tumor shutdown without metastasis besides its antitumor immunity.

Keywords: Hypericin; Hexa Acetyl Hypericin; Colorectal cancer; Photodynamic therapy; Synthetic photosensitizers.