Gelidiella acerosa inhibits lung cancer proliferation

Abstract

BackgroundLung adenocarcinoma is the most common subtype of Non small cell lung cancer in which the PI3K/Akt cascade is frequently deregulated. The ubiquitous expression of the PI3K and the frequent inactivation of PTEN accounts for the prolonged survival, evasion of apoptosis and metastasis in cancer. This has led to the development of PI3K inhibitors in the treatment of cancer. Synthetic PI3K inhibitors undergoing clinical and preclinical studies are toxic in animals. Hence, there is a critical need to identify PI3K inhibitor(s) of natural origin.The current study aims to explore the efficacy of the red algae Gelidiella acerosaon inhibition of cell proliferation, migration and the expression of cell survival genes in lung adenocarcinoma cell line A549.MethodsThe phytoconstituents of Gelidiella acerosa were extracted sequentially with solvents of different polarity, screened qualitatively and quantitatively for secondary metabolites and characterized by GC-MS. The in-vitro studies were performed to check the efficacy of the extract on cell proliferation (MTT assay), cell invasion (scratch assay and colony formation assay), apoptosis (fluorescent, confocal microscopy and flow cytometry) and expression of apoptosis and cell survival proteins including PI3K, Akt and GSK3β and matrix metalloproteinase MMP2 and MMP9 by Western blot method. The antitumor activity of GAE was analyzed in a tumor model of Zebrafish.ResultsThe outcomes of the in vitro analysis showed an inhibition of cell proliferation, induction of apoptosis, inhibition of cell migration and colonization by the crude extract. The analysis of protein expression showed the activation of caspases 3 and Pro apoptotic protein Bax accompanied by decreased expression of Bcl-2 and Bcl-XL. On the other hand, subsequent activation of GSK3β and down regulation of PI3K, Akt were observed. The decreased expression of MMP2 correlated with the antimetastatic activity of the extract. The in vivo studies showed an inhibition of tumor growth by GAE in Zebrafish.ConclusionThe phytoconstituents of algal extract contributed to the anticancer properties as evidenced by in vitro and in vivo studies. These phytoconstituents can be considered as a natural source of PI3K/Akt inhibitor for treatment of cancers involving the PI3K cascade.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2165-1) contains supplementary material, which is available to authorized users.

Gelidiella Acerosacompounds Target NFKB Cascade in Lung Adenocarcinoma

“…1. The antioxidant e cacy of GAE was previously determined by DPPH assay [21] and the outcomes of the current study strongly correlated with our previous observation.This is due to the increased activity of superoxide dismutase and peroxidases which are generally down regulated or inhibited in cancer. The results strongly con rmed the antioxidant e cacy of the algal compounds to detoxify the ROS.…”

“…Furthermore, the upregulation of antiin ammatory marker con rms the anti-in ammatory potential of the algal compounds. Our previous studies [21,22] has revealed the anticancer and antimetastatic properties of the algal extract and this current investigation has revealed the anti-in ammatory property of the extract both underin silicoand in vitro conditions. As in ammation can cause cancer progression, then the inhibition of in ammation must in turn inhibit tumorigenesis.…”

“…The marine red algae are a rich in phytocompounds with varied bioactivities. In an earlier study, [21,22] we analyzed the anticancer and antimetastatic activities of marine red algae Gelidiella acerosa under both in vitro and in vivo conditions. The current study now analyzed the interaction of isolated algal compounds with IkBα-NFKB-p65-p50 complex under in silico, to determine the e cacy of the algal extract on SOD and POX activities in adenocarcinoma cell line A549, to analyze the expression of NFKB, proin ammatory cytokines (TNF α and IL-1β) and anti-in ammatory cytokine IL 10 under in vitro conditions.…”

Phytochemical characterization by GC-MS and in vitro evaluation of antiproliferative and antimigratory studies of Leucas aspera leaf extracts on MDA-MB-231 cell line

“…Extraction of the plant’s phytochemicals was carried out by sequential method as outlined in the published protocol (Begum et al, 2018 ). Thirty grams of plant leaf powder underwent extraction with 100 ml of solvents in increasing order of polarity: hexane, followed by dichloromethane, and finally, ethyl acetate.…”

Zebrafish in Lung Cancer Research

“…Unlike the studies mentioned above, some researchers have opted for adult zebrafish as experimental animals [105][106][107]. In this method, LC cells are injected into the gills or muscle tissue of the zebrafish, and candidate drugs are administered orally.…”