Cytotoxic and Antiproliferative Activity of Polyisoprenoids in Seventeen Mangroves Species Against WiDr Colon Cancer Cells

Abstract

Background: Secondary metabolites from the group of isoprenoid compounds are widely distributed in mangrove plants. Polyisoprenoids (dolichol and polyprenol) are known to have benefits as anticancer agents. The present study was conducted to determine the cytotoxic potential of polyisoprenoids in leaves from seventeen selected mangrove species against colon cancer (WiDr) cells. Methods: Cytotoxic activity was evaluated by MTT assay in vitro using WiDr human colon cancer cells and 3T3 fibroblasts from Swiss albino mouse embryo tissue as controls. Mechanisms of action were approached by assessing apoptosis and the cell cycle using flow cytometry and fluorescence microscopy with annexin V-FITC, as well as expression of Bcl-2 and cyclin D1 by immunocytochemistry. Results: Polyisoprenoids from N. fruticans leaves demonstrated the highest anticancer activity, with an IC 50 of 180.2 µg/mL, as compared to 397.7 µg/mL against 3T3 normal cells. Significant decrease in the expression of Bcl-2 and cyclin D1 was also noted, facilitating apoptosis and arrest of the cell cycle in the G0-G1 phase in WiDr cells. The present study showed for the first time that polyisoprenoids from N. fruticans exhibit concrete anticancer activity in vitro, decreasing cell proliferation and inducing apoptosis in colon cancer cells. Conclusions: Polyisoprenoids isolated from N. fruticans leaves may have promise as a source of anticancer agents.

Effects of polyisoprenoids from Avicennia lanata and Avicennia alba leaves on the gene expression of PI3K, Akt1, mTOR, P53, and EGFR in human colorectal adenocarcinoma WiDr cells using reverse transcription-PCR

“…The simplicia procedure is described briefly; the wet mangrove leaves were sorted to remove dirt; the leaf bones were removed and cleaned from attached leaf spines; the leaves were cut into 3 cm long pieces, after which they were washed under running water, drained, and weighed. Subsequently, the mangrove leaves were dried in a drying cabinet, dry sorted to separate unwanted plant parts and other impurities that were still present, remain in dry simplicia, and weighed and stored in tightly closed plastic containers 8 . The lipid extracts of leaves were refluxed at a temperature of 65°C for 24 h in 86% ethanol containing KOH 2 M. The portions were further saponified and diluted with 2 mg/mL n-hexane.…”

“…Previous research suggests that polyisoprenoids induce cancer cell cycle inhibition in adenocarcinoma of the colon (COLO 320 HSR, WiDr, and LS174 cells) in the G2/M phase and reduce the percentage of Bcl-2 and Bcl-xL 7 . Polyisoprenoids have been previously reported as chemopreventive agents for colon cancer 8 , given that polyisoprenoids in A. lanata leaves have displayed anticancer activity for the same 9 . On the other hand, A. alba contains polyisoprenoids that induce cell cycle, apoptosis, and gene expression of COX-2 in colon cancer cells WiDr 10 .…”

Effects of polyisoprenoids from Avicennia lanata and Avicennia alba leaves on the gene expression of PI3K, Akt1, mTOR, P53, and EGFR in human colorectal adenocarcinoma WiDr cells

“…Selectivity index (SI) was determined from the IC 50 of the polyisoprenoid extract from PAA and PAL leaves in Vero cells versus WiDr cells to exhibit the cytotoxic selectivity of the polyisoprenoid extract, as previously reported 9 . IC 50 was calculated from concentrations that caused death among 50% of the cell population analysed using probit analysis in SPSS version 23 with a significance of 0.05 8 .…”

“…This study also indicated that mangrove polyisoprenoids blocked the development of WiDr colon cancer. Furthermore, our previous studies have shown that polyisoprenoids from mangrove leaves induced apoptosis, decreased cell proliferation, and exhibited anticancer activity [8][9][10] . We on the basis of present and previous studies proposed mechanism of inhibition of cell cycle at G0-G1 phase and enabled the suppression of COX-2 and p53 against WiDr colon cells.…”

“…Previous research suggests that polyisoprenoids induce cancer cell cycle inhibition in adenocarcinoma of the colon (COLO 320 HSR, WiDr, and LS174 cells) in the G2-M phase and reduce the percentage of Bcl-2 and Bcl-xL 7 . Polyisoprenoids have been previously reported as chemopreventive agents for colon cancer 8 , given that polyisoprenoids in A. lanata leaves have displayed anticancer activity for the same 9 . On the other hand, A. alba contains polyisoprenoids that induce cell cycle, apoptosis, and gene expression of cycloogenase-2 (COX-2) in colon cancer cells WiDr 10 .…”