Lathyrol Binds with STAT3 DNA Binding Domain and Induces Apoptosis in Multiple Human Cancer Cells
Lathyrol Binds with STAT3 DNA Binding Domain and Induces Apoptosis in Multiple Human Cancer Cells
Abrar ul Haq1, Shusheng Yin2, Amara Maryam1, Muhammad Khan1*, Hafiz Abdullah Shakir1, Muhammad Akhtar Ali3, Muhammad Irfan4, Muhammad Faisal Maqbool1 and Yongming Li2*
Chemical structure of lathyrol.
Lathyrol decreases cell viability of multiple human cancer cell lines. Cells were cultured in 96-well plates in triplicates and treated with given concentrations of lathyrol overnight. The cell viability was determined using CCK-8 assay kit.
Effect of lathyrol on activation and expression of STAT3 and cleavage of caspase-3. (A) Hep-3B, (B) MHCC97-L, (C) A2780 and (D) taxol-resistant Hey-T30 cells were treated with lathyrol overnight and cell lysates were prepared using RIPA lysis buffer supplemented with 10%PMSF. The cell lysates were subjected to immunoblotting for the expression of p-STAT3, STAT3, and cleaved caspase-3. GAPDH was used a loading control.
A schematic diagram representing natural sources and cellular targets of lathyrol in multiple human cancer cell lines. Semen Euphorbiae is a traditional Chinese medicine prepared from ripen fruits of Euphorbi lathyrus. Lathyrol is the major components of Semen Euphorbiae and Euphorbi lathyrus. Lathyrol binds with DNA binding domain of STAT3 and induces cleavage of caspase-3 in cancer cells to induce apoptosis.
Lathyrol is predicted to bind with DNA binding domain of STAT3. (A) 3D Interaction of lathyrol with crystal structure of STAT3 obtained by using PyMol. (B) 2D diagram obtained by LigPlot+ (version 2.2), showing the hydrogen bond in green dotted lines between lathyrol and different amino acid residues of STAT3.
