Abstract B13: In vitro animal cancer model for assessment of sulfated polysaccharides extract of Ulva lactuca as colon cancer therapeutic and chemopreventive agents

Abstract

Abstract Purpose: Sulfated polysaccharides extract of Ulva lactuca (ULSP) was in vitro assessed as probable chemopreventive and therapeutic agents for colon cancer (CC) comparing with currently used chemotherapy (5-fluorouracil “5-FU” and mitomycin-C “MMC”) using our newly developed in vitro transformed cancerous rat colon epithelial cells. Methods: The present study used an in vitro animal CC model as it resembles human multistage of chromosomal instability type of CC that is located mainly at distal colon. Hence, this model was used for evaluating ULSP by the detection of cytotoxicity against normal and cancerous colon cells and antimetastatic potency. Besides, ULSP efficacy as CC chemopreventive agent was assessed through the detection of CC progression markers; loss of heterozygosity of deleted in colorectal cancer (DCC) and p53, aldehyde dehydrogenase (ALDH) 1B1 expression, activities of ornithine decarboxylase (ODC), cyclooxygenase-2 (COX-2) and alkaline phosphatase (ALP), cellular redox state (Eh), doubling time, and mucin level. Results: The apoptosis-dependent anticancer activity of ULSP (4.9 µg/ml) was revealed at all stages of cancerous distal colon epithelial cells by the formation of apoptotic bodies and DNA fragmentation (above 43%) without affecting normal colon epithelial cells. Also, its inhibitory effect on the invasion of cancerous epithelial and Caco-2 cells (above 49%) was stronger than that of 5-FU+MMC (about 11%). Cells were treated with ULSP before exposure to CC inducers and they showed normal tumor suppressor genes (DCC and p53), normal expression of ALDH1B1, and normal activity of ODC (0.03±0.0004 U/μg) and null activity of COX-2. In addition, their normal pattern of proliferations (doubling time 3 days and Eh 252.7±2.12 mV) and differentiation was confirmed by the maintenance of ALP activity (0.46±0.01 mU/μg) and the secretion of mucin (29.2±0.2 μg/ml) compared to normal and cancerous colon epithelial cells. Conclusion: Our innovative in vitro model of colon cancer have proved that ULSP could have induced apoptosis at all stages of cancerous colon cells, inhibited cancerous cells to metastasize and blocked CC progression without effect on normal epithelial cells comparable to chemotherapy. Citation Format: Marwa Abu-Serie, Maha El Demellawy, Mohamed El-Sayed, Fatma El-Rashidy. In vitro animal cancer model for assessment of sulfated polysaccharides extract of Ulva lactuca as colon cancer therapeutic and chemopreventive agents. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B13.