Sophorolipid Candidates Demonstrate Cytotoxic Efficacy Against 2D And 3D Breast Cancer Models

Abstract

Sophorolipids are biosurfactants derived from the non-pathogenic yeast Starmerella bombicola, with potential efficacy in anti-cancer 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 potential for 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. We screened two sophorolipid candidates and 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.

Molecularly Engineered Surfactin Analogues Induce Nonapoptotic-Like Cell Death and Increased Selectivity in Multiple Breast Cancer Cell Types

“…We expected, based on previous studies by ourselves 36 and others, 35 , 37 , 38 and anticipated that 3D tumor cell aggregates in a spheroid morphology would lead to higher IC 50 values. Hence, dose–response biological activity assays were extended for BT-474 ( Figure 3 A) and MDA-MB-231 ( Figure 3 B) cell lines to 3D tumor aggregates, prepared using liquid-overlay with Matrigel following previous work by our group.…”

“…Hence, dose–response biological activity assays were extended for BT-474 ( Figure 3 A) and MDA-MB-231 ( Figure 3 B) cell lines to 3D tumor aggregates, prepared using liquid-overlay with Matrigel following previous work by our group. 36 , 39 , 40 Briefly, MDA-MB-231 or BT-474 cell lines, selected for their stark differences in morphology and cell receptor presence, were seeded in a 96-well plate in the presence of Matrigel, centrifuged to form 3D tumor spheroids, and allowed to incubate for 4 days. Following 24 h treatment of MDA-MB-231 3D spheroids, the IC 50 value for 1 was 140 μg/mL, representing a 1.7-fold increase over that of 2D monolayer cultures ( Table 5 ).…”

“…Matrigel (2.5% v/v) was added to each well, and, immediately after, the plate was centrifuged for 10 min at 1000 rpm to ensure collection of a cell pellet at the bottom of each well. Plates were incubated, and cell aggregates were cultured over a 4 day maturation period prior to compound testing. ,, Compounds were individually solubilized in 100% DMSO, followed by dilutions to concentrations from 10,000 to 80 μg/mL in 1:2 serial dilutions; 10 μL of each corresponding drug concentration was added to each well in triplicatethus, each concentration has been diluted 10-fold due to the 100 μL of media present in the cell from cell seeding. Care was taken such that the final concentration of DMSO was no more than 1% v/v per well.…”

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.…”