ABSTRACT
Neurada procumbens L. commonly called as sand button, is used as a medicinal herb by Bedouin in the Arabia Peninsula for heart and respiratory functions. This little known plant has not been investigated in detail for its biological activities. Hence, we have made an attempt to investigate the plant for its anticancer activities. Methanol and chloroform extracts of N.procumbens were evaluated for antiproliferative and anticancer activities in HEp-2 and MCF-7 cancer cell lines. Humanforeskin epithelial cells showed an IC50 value of 34 ?g and 149 ?g for chloroform and methanol extracts, respectively. Thechloroform extract of N. procumbens @3 ?g showed 50% reduction of HEp-2 cell population in 24 h, while 5.5 ?g showedsimilar effects in MCF-7 cells. The results of the methanol extracts were little varied, where 49 ?g showed slow inhibitionof HEp-2 cells over a period of 72 h. In another similar observation, 76 ?g of methanol extract inhibited 50% MCF-7 cellproliferation. The concentrations which could inhibit complete turnover of the experimental cancer cell lines at 24 h were>5 ?g and 6 ?g of chloroform extract and > 60 ?g and 80 ?g of methanol extract for HEp-2 and MCF-7, respectively. Themicro therapeutic index of methanol extract in HEp-2 and MCF-7 were 3 and 1.9, while chloroform extract was 11.3 and6.1. This is an initial observation of N. procumbens that shows antiproliferative activities against cancer cell lines.
ABSTRACT
PURPOSE: Anomalies of Akt regulation, including overexpression in lung cancer, impart resistance to conventional chemotherapy and radiation, thereby implicating this kinase as a therapeutic intervention point. A novel scaffold of Akt inhibitors was developed through virtual screening of chemical databases available at Birla Institute of Technology and Science, Pilani, Hyderabad, based on docking studies using Maestro. A benzothienopyrimidine derivative (BIA-6) was identified as a potential lead molecule that inhibited Akt1 enzyme activity with an IC50 of 256 nM. MATERIALS AND METHODS: BIA-6 was tested for in vitro Akt1 inhibition using a fluorescence resonance energy transfer kit. Anti-proliferative activity was tested in NCI-H460, A549, NCI-H1975, and NCI-H2170 cell lines. The effect of the compound on p-Akt (S473) was estimated. RESULTS: BIA-6 allosterically caused a dose dependent reduction of growth of cell lines with a half maximal growth inhibition (GI50) range of 0.49 muM to 6.6 muM. Cell cycle analysis indicated that BIA-6 caused a G1 phase arrest at < 100 nM but led to apoptosis at higher doses. BIA-6 also exhibited synergism with standard chemotherapeutic agents. CONCLUSION: BIA-6 is a novel, allosteric Akt inhibitor with potent anti-cancer activity in lung cancer cell lines, that effectively blocks the phosphoinositide-3 kinase/Akt pathway with a high margin selectivity towards normal cells.