Anticancer metabolites from lichens

Abstract

To combat cancer effectively through discovery of novel compounds, the present study newlinewas aimed at lichens as natural sources. Lichens, which are rich sources of secondary newlinemetabolites with medicinal relevance, were evaluated in the current study for in vitro newlineanticancer, anti-proliferative, and in ovo antiangiogenic profiles. The promising lichens newlinewere identified as Ramalina farinacea, Parmotrema tinctorum, and Parmotrema newlinecristiferum. The highly effective cytotoxicities of the TLC-purified fractions L2F3, newlineL3F1, and L5F3 were evidenced by the MTT assay, resulting in significant reduction in newlineliver, cervical, and breast cancer cell viabilities with IC50 values ranging between 3.98 newline6.57 and#956;g/mL. The anticancer effects were further supported by trypan blue, LDH, and newlineDNA fragmentation assays. Lichen fraction treatment successfully induced apoptosis in newlinethe cancer cells through the activation of the caspase cascade, up-regulation of the newlineapoptosis regulatory genes p53, PTEN, and Bax, along with downregulation of Bcl-2. newlineAccumulation of apoptotic cells in the Sub-G1 phase was evidenced by flow cytometry newlineresults. In order to improve their efficacy, a combination of lichen fractions was newlinestatistically (RSM) optimised to find the most effective combination, which revealed LC7 newlineas the best. Significant inhibition of angiogenesis was found by the lichen fractions and newlineLC7 when analyzed through in ovo YSM assay. As evidence for their anti-proliferative newlinepotential, lichen fractions and LC7 significantly reduced the number and size of colonies newlinein cancer cells, with the combination LC7 showing significantly greater inhibition. The newlinestudy also confirmed the non-toxic nature of the lichen fractions towards the normal cells newline lymphocytes and Vero cells. The characterization through GC MS analysis, indicated newlinethe presence of bioactive compounds, such as atraric acid, orcinol, methyl orsellinate, and newlinelupeol. The lichen fractions combination, LC7 was the first combination approach, with newlineremarkably higher anticancer efficacies and lower toxic side effects newline