oleuropein and Lung-Neoplasms

Oleuropein (OP) is a bioactive compound derived from plants of the genus Oleaceae exhibiting antitumor properties in several human cancers, including non-small-cell lung cancer (NSCLC). Recent evidence suggests that OP has proapoptotic effects on NSCLC cells via the mitochondrial apoptotic pathway. However, the exact molecular mechanisms behind the apoptogenic action of OP in NSCLC are still largely unknown. Glyoxalase 2 (Glo2) is an ancient enzyme belonging to the glyoxalase system involved in the detoxification of glycolysis-derived methylglyoxal. However, emerging evidence suggests that Glo2 may have also nonenzymatic roles in some malignant cells. In the present study, we evaluated whether and how Glo2 participated in the proapoptotic effects of OP in NSCLC A549 cells. Our results indicate that OP is able to induce apoptosis in A549 cells through the upregulation of mitochondrial Glo2 (mGlo2), mediated by the superoxide anion and Akt signaling pathway. Moreover, our data shows that the proapoptotic role of mGlo2, observed following OP exposure, occurs via the interaction of mGlo2 with the proapoptotic Bax protein. Conversely, OP does not alter the behavior of nonmalignant human BEAS-2B cells or mGlo2 expression, thus suggesting a specific anticancer role for this bioactive compound in NSCLC. Our data identify a novel pathway through which OP exerts a proapoptotic effect in NSCLC and suggest, for the first time, a novel, nonenzymatic antiapoptotic role for this ancient enzyme in NSCLC.

Topics: A549 Cells; Apoptosis; bcl-2-Associated X Protein; Carcinoma, Non-Small-Cell Lung; Humans; Iridoid Glucosides; Iridoids; Lung Neoplasms; Mitochondria; Proto-Oncogene Proteins c-akt; RNA Interference; RNA, Small Interfering; Signal Transduction; Superoxide Dismutase; Superoxides; Thiolester Hydrolases; Up-Regulation

Topics: Apoptosis; Cell Line, Tumor; Enzyme Activation; Gene Expression Regulation, Neoplastic; Humans; Iridoid Glucosides; Iridoids; Lung Neoplasms; MAP Kinase Signaling System; Mitochondria; Neoplasm Proteins; p38 Mitogen-Activated Protein Kinases

The current systemic treatments of the various solid tumors involve Cisplatin (CIS)-based chemotherapy. Due to its cytotoxicity, this approach is limited. Moreover, the safety of CIS is only discussed especially in breast and stomach cancers. Therefore, we, for the first time, explored the restorative efficacy of oleuropein (OLE), in stomach and lung injuries induced by CIS. Sprague-Dawley rats were divided into eight groups: control CIS, OLE and CIS + OLE. Single dose of (7 mg/kg) CIS was administered intraperitoneally to CIS and CIS + OLE groups. After 24 h, 50, 100 and 200 mg/kg OLE was given for three consecutive days to OLE and CIS + OLE groups. The 8-OH-dG, total oxidative/antioxidant status (TOS/TAS) and malondialdehyde (MDA) levels were evaluated and histopathological analyses were performed on the studied tissues. The results indicated that CIS significantly increased 8-OH-dG, MDA and TOS levels and caused severe tissue damages. However, high dose of OLE induced a significant decrease in the 8-OH-dG, MDA levels, an increase in TAS levels and it restores CIS-induced tissue damages. We hope that the results of this study will provide an impetus for future studies on novel therapeutic strategies including the protective use of oleuropein in gastric and lung cancers due to chemotherapy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Antioxidants; Cisplatin; Deoxyguanosine; DNA Damage; Iridoid Glucosides; Iridoids; Lung Neoplasms; Male; Malondialdehyde; Molecular Structure; Oxidative Stress; Rats; Rats, Sprague-Dawley; Stomach Neoplasms