A Tropical Lichen, Dirinaria consimilis Selectively Induces Apoptosis in MCF-7 Cells through the Regulation of p53 and Caspase-Cascade Pathway.

BACKGROUND: Breast cancer is the most leading cause of death, with 49.9% of crude incidence rate and 12.9% of crude mortality rate. Natural resources have been extensively used throughout history for better and safer treatment against various diseases. OBJECTIVES: The present study was aimed to investigate the antioxidant and anticancer potential of a tropical lichen Dirinaria consimilis (DCME) and its phytochemical analysis. METHODS: The DCME was preliminarily evaluated for ROS, and RNS scavenging potential. Furthermore, DCME was evaluated for in vitro anticancer activity through cell proliferation assay, cell cycle analysis, annexin V/PI staining, morphological analysis, and western blotting study. Finally, the HPLC and LC-MS analyses were done to identify probable bioactive compounds. RESULTS: The in vitro antioxidant studies showed promising ROS, and RNS scavenging potential of DCME. Moreover, the in vitro antiproliferative study bared the cytotoxic nature of DCME towards MCF-7 (IC50 - 98.58 ± 6.82µg/mL) and non-toxic towards WI-38 (IC50 - 685.85 ± 19.51µg/mL). Furthermore, the flow-cytometric analysis revealed the increase in sub G1 population as well as early apoptotic populations dose-dependently. The results from confocal microscopy showed the DNA fragmentation in MCF-7 upon DCME treatment. Finally, the western blotting study revealed the induction of tumor suppressor protein, p53, which results in increasing the Bax/Bcl-2 ratio and activation of caspase-cascade pathways. CONCLUSION: The activation of caspase-3, -8, -9 and PARP degradation led us to conclude that DCME induces apoptosis in MCF-7 through both intrinsic and extrinsic mechanisms. The LC-MS analysis showed the presence of various bioactive compounds.

An Indian Desert Shrub 'Hiran Chabba', Farsetia hamiltonii Royle, Exhibits Potent Antioxidant and Hepatoprotective Effect Against Iron- Overload Induced Liver Toxicity in Swiss Albino Mice.

BACKGROUND: Farsetia hamiltonii Royle, also known as Hiran Chabba grows in desert regions. It is widely used as folk medicine to treat joint pains, diarrhea and diabetes. However, its antioxidant and iron chelation abilities both in vitro and in vivo have not yet been investigated. METHODS: The 70% methanolic extract of F. hamiltonii (FHME) was investigated for its free radical scavenging and iron chelation potential, in vitro. An iron-overload situation was established by intraperitoneal injection of iron-dextran in Swiss albino mice, followed by oral administration of FHME. Liver damage and serum parameters due to iron-overload were measured biochemically and histopathologically to test iron-overload remediation and hepatoprotective potential of FHME. Phytochemical analyses were performed to determine its probable bioactive components. RESULTS: FHME showed promising antioxidant activity, scavenged various reactive oxygen and nitrogen species and chelated iron in vitro. FHME reduced liver iron, serum ferritin, normalized serum parameters, reduced oxidative stress in liver, serum and improved liver antioxidant status in ironoverloaded mice. It also alleviated liver damage and fibrosis as evident from biochemical parameters and morphological analysis of liver sections. The phytochemical analyses of FHME reflected the presence of alkaloids, phenols, flavonoids and tannins. HPLC analysis indicated presence of tannic acid, quercetin, methyl gallate, catechin, reserpine, ascorbic acid and gallic acid. CONCLUSION: Based on the experimental outcome, FHME, an ethnologically important plant can be envisaged as excellent antioxidant and iron chelator drug capable of remediating iron-overload induced hepatotoxicity and the bioactive compounds present in FHME might be responsible for its efficacy.