Identification of steroidal saponins from Tribulus terrestris and their in silico docking studies.

Tribulus terrestris is known to possess many pharmacological properties, most notably its anticancer activities, owing to its rich steroidal saponin contents. Even though many reports are available elucidating the anticancer potential of the herb, we, for the very first time have attempted to isolate and identified the active compound present in seed crude saponin extract and confers its in silico docking ability with various cellular targets proteins. High performance thin layer chromatography confirms the presence of active saponins in leaf and seed saponin extracts which were further fractionated by silica gel column chromatography. Fractions collected were assessed for cytotoxicity on human breast cancer cells. High resolution liquid chromatography and mass spectroscopy was employ to identify the active components present in fraction with highest cytotoxicity. Intriguingly, Nautigenin type of steriodal saponin was identified to present in the active fraction of seed extract (SF11) and the identified compound was further analyzed for its in silico docking interaction using PyRx AutodockVina. Docking studies revealed the high binding affinity of Nuatigenin at significant sites with apoptotic proteins Bcl-2, Bax, caspase-3, caspase-8, p53 and apoptosis inducing factor along with cell surface receptors estrogen receptor, projesterone receptor, epidermal growth factor receptor, and human epidermal growth factor receptor-2. Thus, the conclusions were drawn that saponin fraction of Tribulus terrestis possesses active compounds having anticancer property and specifically, Nuatigenin saponin can be considered as an important therapeutic drug for the breast cancer treatment.

Anti-Metastatic Effects of Lupeol via the Inhibition of MAPK/ERK Pathway in Lung Cancer.

BACKGROUND AND OBJECTIVE: ERK pathway is one of the most crucial pathways in lung cancer metastasis. Targeting its pathway is decisive in lung cancer research. Thus, this study demonstrated for the first time for significant and selective anti-metastatic effects of lupeol against lung cancer A549 cells via perturbations in the ERK signaling pathway. MATERIALS AND METHODS: Human protein targets of lupeol were predicted in silico. Migration and cytotoxicity assays were carried out in vitro. Expression levels of proteins Erk1/2 and pErk1/2 were ensured using Enzyme- Linked Immunosorbent Assay (ELISA). Semi-quantitative RT-PCR technique was used to estimate changes in crucial mesenchymal marker gene expression levels of N-cadherin and vimentin. RESULTS: Lupeol was found to target ERK and MEK proteins effectively. Despite having no cytotoxic effects, lupeol also significantly inhibited cell migration in A549 cells with decreased expression of the pErk1/2 protein along with N-cadherin and vimentin genes. CONCLUSION: Lupeol inhibits cell migration, showed no cytotoxic effects on A549 cells, decreased pErk1/2 and EMT gene expression. Thus, it can serve as a potential ERK pathway inhibitor in lung cancer therapeutics.

In silico docking studies of Lupeol with MAPK pathway proteins- Raf-1, MEK & ERK.

OBJECTIVE: Lupeol, A triterpenoid found in variety of plants is reported to have beneficial medicinal effects on several ailments. Lupeol is also found to show inhibitory effect on proliferation of breast cancer cells. Metastasis is considered to be a major cause for worldwide deaths related to cancer. Ras related MAPK Signaling Pathway is one of the crucial pathways leading to metastasis. Lupeols binding possibility with Ras is already reported. In present study, Interaction between with downstream proteins of Ras- MAPK pathway, Raf ,MEK ,ERK1/2 and their corresponding domains are studied using STRING Database and their structures are retrieved in PDB Format. Lupeols binding affinity with downstream proteins of these signaling proteins at their interacting domains are analyzed. Here in silico docking approach to identify binding sites of each of these proteins with Lupeol is used. FDA approved standard drug molecule CH5126766 was used as reference ligand. Lupeol shows potent binding at significant sites with extremely high affinity. Since it binds with all the proteins involved in the pathway with high efficiency it is an important compound which can be developed as a therapeutic molecule.