Pycnogenol Induces Nuclear Translocation of Apoptosis-inducing Factor and Caspase-independent Apoptosis in MC-3 Human Mucoepidermoid Carcinoma Cell Line

Abstract

Background:Pycnogenol is extracted from the pine bark of a tree known as Pinus pinaster that has variety biological effects. However, its anticancer activity has not yet been completely studied. The aim of this study is to investigate anticancer effect of pycnogenol in MC-3 human mucoepidermoid carcinoma (MEC) cell line.Methods:We describe the effect of anti-cancer of pycnogenol in MC-3 human oral MEC cells using trypan blue exclusion assay, 3-(4,5-dimethylthiazol-2-yl)-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) assay, Western blot, preparation of cytosolic and nuclear fractions, immunocytochemistry and reverse transcriptase polymerase chain reaction.Results:Pycnogenol significantly decreased cell viability and also induced caspase-independent apoptosis. We confirmed that pycnogenol induced the translocation of apoptosis-inducing factor into nucleus and regulated apoptosis. Also, Bak protein stability was partly enhanced by pycnogenol to elevate the expression level of Bak protein.Conclusions:Overall, pycnogenol may be a fascinating therapeutic drug candidate for the treatment of MEC.

An <i>In Vitro</i> Study on the Interactions of Pycnogenol^® with Cisplatin in Human Cervical Cancer Cells

“…The possible mechanism underlying the cytotoxic effect of PYC has been associated with apoptosis. 16,17 In the study investigating the apoptotic effects of PYC, PYC induced apoptosis in human fibrosarcoma cells (HT1080), using flow cytometric analysis and RNA microarray. 16 In another study, it was reported that PYC significantly decreased cell viability and also induced caspase-independent apoptosis.…”

“…Furthermore, PYC induced the translocation of apoptosis-inducing factor into the nucleus and regulated apoptosis. 17 In a study investigating the antitumor effect of PYC, the IC 50 values of PYC in human leukemia cells (HL-60, U937, and K562) were reported to be 150 µg/mL (~516.8 µM), 40 µg/ mL (~137.8 µM), and 100 µg/mL (~344.5 µM), respectively, for 24 h incubation, by propidium iodide exclusion. 18 In another study, in which the apoptotic effect of PYC in human oral squamous carcinoma (HSC-3) cells was investigated by the MTS assay, the IC 50 value of PYC was reported as 20 µg/mL (~68.9 µM) for 24 h incubation.…”

Pycnogenol Cytotoxicity in Pancreatic INS‐1E β cells Induced by Calcium Dysregulation

“…However, adverse effects of Pyc were observed in an in vitro model of lens cataract formation, accompanied by elevation of [Ca 2+ ] i and mitochondrial death in the cells of lens fibers (Trevithick et al ., ). Diverse apoptotic mechanisms have been suggested for Pyc also in a number of cancer cell lines (Huang et al ., ; Park and Kim, ; Yang et al ., , ). The pathway of mitochondria‐dependent apoptotic cell death has been considered to be both caspase‐dependent (Huang et al ., ; Park and Kim, ; Yang et al ., ) and caspase‐independent (Yang et al ., ).…”

“…Diverse apoptotic mechanisms have been suggested for Pyc also in a number of cancer cell lines (Huang et al ., ; Park and Kim, ; Yang et al ., , ). The pathway of mitochondria‐dependent apoptotic cell death has been considered to be both caspase‐dependent (Huang et al ., ; Park and Kim, ; Yang et al ., ) and caspase‐independent (Yang et al ., ). In addition, reactive oxygen species generation (Park and Kim, ; Yang et al ., ), increase of Bak protein expression (Yang et al ., ), and translocation of apoptosis‐inducing factor into nucleus (Yang et al ., ) may play a role in apoptosis.…”

“…Paradoxically, Pyc was also reported to show cytotoxicity in the in vitro model for hyperglycemic lens cataract formation, accompanied by intracellular Ca 2+ increase in lens fiber cells (Trevithick et al ., ). In addition, cytotoxic and proapoptotic effects of Pyc were shown also in various cancer cell lines, including human squamous cell carcinoma HSC‐3 cells, human mucoepidermoid carcinoma MC‐3 cells, HL‐60, U937, and in K562 human leukemia cells (Huang et al ., ; Yang et al ., , ). Pycnogenol induced apoptosis in human fibrosarcoma cells in a reactive oxygen species‐dependent manner, and in addition, more apoptotic cells were found in human fibrosarcoma cells displaying increased DNA damage than in human fibroblastoma cells.…”