Sophorolipid Candidates Demonstrate Cytotoxic Efficacy against 2D and 3D Breast Cancer Models

Abstract

Sophorolipids are biosurfactants derived from the nonpathogenic yeasts such as Starmerella bombicola with potential efficacy in anticancer applications. Simple and cost-effective synthesis of these drugs makes them a promising alternative to traditional chemotherapeutics, pending their success in preliminary drug-screening. Drug-screening typically utilizes 2D cell monolayers due to their simplicity and ease of high-throughput assessment. However, 2D assays fail to capture the complexity and 3D context of the tumor microenvironment and have consequently been implicated in the high percentage of drugs investigated in vitro that later fail in clinical trials. Herein, we screened two sophorolipid candidates and a clinically-used chemotherapeutic, doxorubicin, on in vitro breast cancer models ranging from 2D monolayers to 3D spheroids, employing optical coherence tomography to confirm these morphologies. We calculated corresponding IC50 values for these drugs and found one of the sophorolipids to have comparable toxicities to the chemotherapeutic control. Our findings show increased drug resistance associated with model dimensionality, such that all drugs tested showed that 3D spheroids exhibited higher IC50 values than their 2D counterparts. These findings demonstrate promising preliminary data to support the use of sophorolipids as a more affordable alternative to traditional clinical interventions and demonstrate the importance of 3D tumor models in assessing drug response.

Synergistic Treatment of Breast Cancer by Combining the Antimicrobial Peptide Piscidin with a Modified Glycolipid

“…41 We recently reported a study in which cultured MDA-MB-231 breast cancer cells were dosed individually with DLSL (IC 50 = 20 μM) and diacetylated SL ethyl ester (SL-EE-D) (IC 50 = 33 μM). 27 These results highlight that natural and modified SLs can provide anticancer activity. Here, we describe how antagonistic interactions can be used to reduce the cytotoxicity of an SL ester toward a nontumorigenic cell line while increasing its activity toward cancer cell lines.…”

“…Sophorolipids (SLs) are natural glycolipid biosurfactants produced in high volumetric titers (∼200 g/L) from the nonpathogenic yeast Starmerella bombicola. , SL esters are a versatile family of synthetically modified SLs. − They are synthesized by an alcoholysis reaction between natural diacetylated lactonic sophorolipid (DLSL) and an alcohol under alkaline conditions. , Of particular interest herein is SL-HE (Figure ), where the primary alcohol used is n -hexanol, and a concurrent deacetylation of sophorose occurs due to alkaline reaction conditions …”

“…SLs possess many biological properties, including anticancer, ,,− anti-inflammatory, ,− antisepsis, , and immunomodulatory activities . The literature on SLs indicates that DLSL can induce increased reactive oxygen species (ROS) on MDA-MB-231 cells, as well as apoptosis in ovarian (HeLa) tumorigenic cells, through activation of an ER-mediated pathway .…”

“…The sophorolipid analogues SL-methyl and SL-ethyl ester were reported to cause pancreatic cancer cell cancer death by a necrotic pathway . We recently reported a study in which cultured MDA-MB-231 breast cancer cells were dosed individually with DLSL (IC 50 = 20 μM) and diacetylated SL ethyl ester (SL-EE-D) (IC 50 = 33 μM) . These results highlight that natural and modified SLs can provide anticancer activity.…”