Subcutaneous phosphatidylcholines (PPCs) injection was promoted as efficacious alternative medical procedure to liposuction for local fat deposit removal. It has been shown that PPCs able to induce apoptosis of adipocyte observed by clear evidence of apoptotic proteins involvement, including cleavage of caspase-8. Cleavages of caspase-8 were basically known involved in Fas-death induce pathway in apoptosis. However, whether PPCs has Fas ligand (FasL) agonistic activity that may directly activates Fas receptor (FasR) remains unknown.

Separation using reverse phase-high performance liquid chromatography of high purity of soya PPC showed 6 peaks that may refers to various types of PPCs with different fatty acyl chain combination at sn-1 and sn-2 position in its glycerol backbone.  It has been reported that PPCs from soya bean are isolated as mixed compound of PPC with palmityl, stearyl, oleyl, linoleyl and linolenyl distributed at sn-1 and oleyl, linoleyl and linolenyl at sn-2 position on the glycerol backbone resulted 15 types of PPC.

In this study, authors have checked FasL agonistic property from various types of soya PPCs by molecular docking to FasR.  The author also compared interaction between PPCs and FasR to the interaction between genistein and FasR. Genistein is estrogenic soy isoflavone that has a pro-apoptotic, antiproliferative and anti-adipogenic activites on adipocytes. FasR molecular 3D model was obtained from RCSB Protein Data Bank with PDB ID: 3TJE. Active site candidates in FasR for ligand binding was determined using CastP Site Finder. Dockings were performed surrounded the interest region positioned at -6.693, 6.965 and 12.774 as x, y, z coordinates. We found that Tyr 75, Arg 86, Arg 89, Asn 108, Cys 111, and Cys 124 of FasR as binding residues for PPCs, while genistein binds to FasR in Arg 89 residue.

1,2-Dioleyl-sn-glycero-3-phosphocholine were found as compounds with the strongest binds to FasR with binding afinity as much as -5,3 kcal/mole, while 1-stearyl-2-linolenyl-sn-glycero-3-phosphocholine the weakest binds to FasR with the lowest binding affinity, which is 4.1 kcal/mole. Compare to genistein with binding affinity to FasR as much as -6.9 kcal/mole, PPCs has lower binding affinity to FasR.

We confirmed in silico study’s result with toxicity assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide (MTT) method. We test various concentration of soya PPCs begin form 0 mg/ml to 1 mg/ml to the adipose derived stem cell (ADSCs), and see the cells viability. From MTT assay, it has been showed that PPCs have tendency to reduce ADSCs viability with lower toxicity compared to PPCs solution that contains 2% of sodium deoxycholate (SD), necrotic cell’s agent. We conclude that soya-PPCs may serves as potent pro-apoptotic agent in certain dose and need to be further developed for gaining a new effective PPCs formulation and with minimal side effect rather than PPC/SD formulation that we already tested for 9 years as clinical medication.