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*
ABSTRACT
Lathyrol, a natural diterpenoid molecule is one of the major components of Semen Euphorbiae, a famous traditional Chinese medicine with a long history of clinical use in China. Very recently, lathyrol has been reported to inhibit the growth and induce apoptosis in lung cancer cells. However, the anticancer activity of lathyrol remains largely unknown in various human cancers. The present study was designed to evaluate lathyrol for its broad-spectrum anticancer activity and binding affinity with STAT3 DNA binding domain. Using CCK-8 assay kit, we showed that lathyrol reduced the cell viability of Hep-3B, MHCC97-L, A2780 and taxol resistant Hey-T30 cells in a dose-dependent fashion. Using Molecular docking study, we found that lathyrol exhibits strong binding interactions with STAT3 DNA binding domain through hydrogen bonding and hydrophobic interactions with various amino acid residues of STAT3. Using immunoblotting, we found that lathyrol did not inhibit STAT3 phosphorylation and dimerization. Moreover, we showed that lathyrol induces apoptosis as evident from a remarkably increased expression of cleaved caspase-3 in all four cancer cell lines. Taken together, our findings suggest that lathyrol is a potent STAT3 DNA binding domain inhibitor and exhibits a broadspectrum anticancer activity.
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