Abstract 2294: Sophorolipid-mediated inhibition of colorectal tumor cell growth in vitro and in vivo
Authors: Callaghan Breedge , Roelants Sophie , Baccile Niki , Lydon Helen , Van Bogaert Inge , Banat Ibrahim M. , Marchant Roger , Mitchell Christopher A. 
Published: August 2015

Background: Sophorolipids (SL), are amphiphilic biosurfactant molecules which consist of a sophorose molecule with 2 variable chain length (C10 - C22) They contain double bonds at the 3” 4” positions and fatty acids at the 1” positions. SL exist in either a lactonic (SLL; open ring) or acidic (SLA; closed ring) forms. SL is produced in crude mixtures by the yeast Candidia bombicola in economically viable amounts, with variable levels of anti-proliferative activity on tumour cell lines in vitro. As biosurfactants are well tolerated in the GI tract and currently used in a variety of food products, we tested the hypotheses that purified forms of either SLL or SLA have differential effects on colo-rectal tumour versus “normal” cells as well as in a well-established model of pre-cancerous lesions; viz the Apcmin+/− mouse.

Methodology: The colo-rectal cancer cell lines HT29, HT115, HCT116, Caco-2 in addition to CCD-841 colonic epithelium and MRC5 lung fibroblasts were exposed to 10 - 100 μg/ml of either SLL or SLA (96% or 94%) pure respectively by HPLC/MS analysis) for 24 hours following serum starvation and an MTT assay performed. The mechanism of cell death in cell lines was assessed by acridine orange/ethidium bromide staining followed by microscopic examination. Five-week old APCmin+ mice or wild-type littermate mice were treated orally with 50mg/kg of either SLL or SLA, or vehicle-only control every other day for 14 weeks. Weights, water and food consumption were measured on a daily basis. On completion of the experiment, mice were euthanized, the digestive tract was excised, washed and fixed with 10% BFS. Polyp size, number and location were recorded and samples were blocked for paraffin embedding, sectioning and H&E/immunofluorescence staining and analysis.

Results and Discussion: In vitro, SLL caused a decrease in colorectal cancer cell viability at &gt;70μg/ml. However, it also caused an unfavourable effect on the colonic epithelium and lung fibroblast cell lines by reducing cell viability at a lower concentration (&lt;10μg/ml). In-vivo, SLL treatment exacerbated the growth of polyps along the digestive tract of APCmin+ mice. SLL treatment resulted in an increase in polyp number and size compared to vehicle treated APCmin+ mice. SLL treated mice presented with reduced haematocrits (28.5% vs 34.5% p&lt;0.03) and increased spleen weights (0.56g vs 0.70g p&lt;0.01) compared to vehicle treated control APCmin+ mice.

SLA induced a dose dependent decrease in cell viability of colo-rectal cancer cell lines (20μg/ml) without affecting the viability of the colonic epithelial and lung cell lines. SLA selectively induced cell death in the colo-rectal cancer cells by means of necrosis. However the effects of SLA in vivo are yet to be established.

Contrary to current literature, purified SLA appears to have an advantage over the SLL form in vitro. To date, this is the first study investigating anti-cancer effects of sophorolipids in vivo.

Citation Format: Breedge Callaghan, Sophie Roelants, Niki Baccile, Helen Lydon, Inge Van Bogaert, Ibrahim M. Banat, Roger Marchant, Christopher A. Mitchell. Sophorolipid-mediated inhibition of colorectal tumor cell growth in vitro and in vivo. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2294. doi:10.1158/1538-7445.AM2015-2294