An Antioxidant Extract of Tropical Lichen,Parmotrema reticulatum, Induces Cell Cycle Arrest and Apoptosis in Breast Carcinoma Cell Line MCF-7

Abstract

This report highlights the phytochemical analysis, antioxidant potential and anticancer activity against breast carcinoma of 70% methanolic extract of lichen, Parmotrema reticulatum (PRME). Phytochemical analysis of PRME confirms the presence of various phytoconstituents like alkaloids, carbohydrates, flavonoids, glycosides, phenols, saponins, tannins, anthraquinones, and ascorbic acid; among which alkaloids, phenols and flavonoids are found in abundant amount. High performance liquid chromatography (HPLC) analysis of PRME revealed the presence of catechin, purpurin, tannic acid and reserpine. Antioxidant activity was evaluated by nine separate methods. PRME showed excellent hydroxyl and hypochlorous radical scavenging as well as moderate DPPH, superoxide, singlet oxygen, nitric oxide and peroxynitrite scavenging activity. Cytotoxicity of PRME was tested against breast carcinoma (MCF-7), lung carcinoma (A549) and normal lung fibroblast (WI-38) using WST-1 method. PRME was found cytotoxic against MCF-7 cells with an IC50 value 130.03±3.11 µg/ml while negligible cytotoxicity was observed on A549 and WI-38 cells. Further flow cytometric study showed that PRME halted the MCF-7 cells in S and G2/M phases and induces apoptosis in dose as well as time dependent manner. Cell cycle arrest was associated with downregulation of cyclin B1, Cdk-2 and Cdc25C as well as slight decrease in the expression of Cdk-1 and cyclin A1 with subsequent upregulation of p53 and p21. Moreover PRME induced Bax and inhibited Bcl-2 expression, which results in increasing Bax/Bcl-2 ratio and activation of caspase cascade. This ultimately leads to PARP degradation and induces apoptosis in MCF-7 cells. It can be hypothesised from the current study that the antioxidant and anticancer potential of the PRME may reside in the phytoconstitutents present in it and therefore, PRME may be used as a possible source of natural antioxidant that may be developed to an anticancer agent.

A Study on Epiphytic Lichens From Prunus Persica

“…Several reports have analyzed similar results, thereby grounding lichen compounds as an alternative drug source for treating diseases caused due to free radicals [26,27].…”

In vitroantitumor activities of the lichen compounds olivetoric, physodic and psoromic acid in rat neuron and glioblastoma cells

“…GBM occurs in the nervous system and, therefore, it is difficult to treat this disease. As central nervous system does not have regenerative capabilities in contrast to other organ systems and if it is damaged, it can be devastating (Goldlust et al 2008).…”

“…The first symptoms resulting from this pressure are headache and dizziness. Loss of sensation and movement occurring on one side of the body, speech disorders, visual disturbances (blurred vision, double vision) and cognitive disorders are other GBM symptoms (Goldlust et al 2008;Urbańska et al 2014).…”

“…They were reported to be effective in the treatment some diseases such as tuberculosis (Vartia 1973), hemorrhoids and dysentery (Dülger et al 1998). Furthermore, antibacterial (Kosanić & Ranković 2011;Kosanić et al 2013Kosanić et al , 2014Grujičić et al 2014), antiviral (Karagöz & Aslan 2005), antiinflammatory (Süleyman et al 2002(Süleyman et al , 2003Halici et al 2005;Odabasoglu et al 2006), antioxidant (Gülçin et al 2002;Aslan et al 2006;Paudel et al 2012;Ghate et al 2013;Grujičić et al 2014), antimutagenic and antigenotoxic activities (Zeytinoglu et al 2008;Agar et al 2010;Alpsoy et al 2011;Kotan et al 2011) of the lichens were reported.…”

“…Similarly, anticancer activities of different lichens on various organs have recently been tested with many studies and positive results have been obtained (Cheng et al 2013;Ghate et al 2013;Kosanić et al 2013Kosanić et al , 2014Singh et al 2013;Celikler Kasimogullari et al 2014;Grujičić et al 2014).…”