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Abstract. Oleuropein could inhibit growth and/or induce apoptosis in several cancer cell lines. In this study, we investigate how oleuropein strongly induces apoptotic cell death in HeLa human cervical carcinoma cells. Oleuropein induced HeLa cells apoptosis as demonstrated by induction of a sub-G 1 peak in flow cytometry and apoptosis-related morphological changes observed by fluorescence microscopy after being stained by Hoechst 33324. The results also showed that 150 -200 mM oleuropein-treated HeLa cells were arrested at the G 2 /M phase. Western blot analysis revealed that the phosphorylated ATF-2, c-Jun NH 2 -terminal kinase (JNK) protein, p53, p21, Bax, and cytochrome c protein in the cytoplasm significantly increased in a dose-dependent manner after treatment of oleuropein for 24 h. Additionally, increasing levels of Bax in response to JNK/SPAK signaling, which formed mitochondrial membrane channels, accounted for releasing of cytochrome c and activation of caspase-9 and -3. SP600125 (20 mM), a JNK 1/2 inhibitor, markedly suppressed the formation of apoptotic bodies and JNK activation induced by oleuropein at 200 mM. Thus, oleuropein-induced apoptosis was activated by the JNK/SPAK signal pathway. The result shows that oleuropein holds promise as a potential chemotherapeutic agent for the treatment of HeLa cells.

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Genipin, a compound derived from Gardenia jasminoides Ellis fruits, has been used over the years in traditional Chinese medicine to treat symptoms of type 2 diabetes. However, the molecular basis for its antidiabetic effect has not been fully revealed. In this study, we investigated the effects of genipin on glucose uptake and signaling pathways in C 2 C 12 myotubes. Our study demonstrates that genipin stimulated glucose uptake in a time-and dose-dependent manner. The maximal effect was achieved at 2 h with a concentration of 10 mM. In myotubes, genipin promoted glucose transporter 4 (GLUT4) translocation to the cell surface, which was observed by analyzing their distribution in subcellular membrane fraction, and increased the phosphorylation of insulin receptor substrate-1 (IRS-1), AKT, and GSK3b. Meanwhile, genipin increased ATP levels, closed K ATP channels, and then increased the concentration of calcium in the cytoplasm in C 2 C 12 myotubes. Genipin-stimulated glucose uptake could be blocked by both the PI3-K inhibitor wortmannin and calcium chelator EGTA. Moreover, genipin increases the level of reactive oxygen species and ATP in C 2 C 12 myotubes. These results suggest that genipin activates IRS-1, PI3-K, and downstream signaling pathway and increases concentrations of calcium, resulting in GLUT4 translocation and glucose uptake increase in C 2 C 12 myotubes.

Abstract. Genipin, an active constituent of Gardenia fruit, has been reported to show an antitumor effect in several cancer cell systems. Here, we demonstrate how genipin exhibits a strong apoptotic cell death effect in human non-small-cell lung cancer H1299 cells. Genipin-mediated decrease in cell viability was observed through apoptosis as demonstrated by induction of a sub-G 1 peak through flow cytometry, DNA fragmentation measured by TUNEL assay, and cleavage of poly ADP-ribose-polymerase. During genipin-induced apoptosis, the mitochondrial execution pathway was activated by caspase-9 and -3 activation as examined by a kinetic study, cytochrome c release, and a dose-dependent increase in Bax/Bcl-2 ratio. A search for the downstream pathway reveals that genipin-induced apoptosis was mediated by an increase in phosphorylated p38MAPK expression, which further activated downstream signaling by phosphorylating ATF-2. SB203580, a p38MAPK inhibitor, markedly blocked the formation of TUNEL-positive apoptotic cells in genipin-treated cells. Besides, the interference of p38MAPK inhibited Bax expression and cytochrome c release. Altogether, our observations imply that genipin causes increased levels of Bax in response to p38MAPK signaling, which results in the initiation of mitochondrial death cascade, and therefore it holds promise as a potential chemotherapeutic agent for the treatment of H1299 cells.

The large infrared lateral photovoltaic effect (LPE) based on semiconductor structures has been a challenge for a long time because the light in this region is hard to be absorbed. In this study, we report an unusual infrared laser induced LPE observed in sputtered Cu(2)O thin films. The maximum open-circuit lateral photovoltage can reach up to a remarkable value of 30.6mV under irradiation of Ti: Sapphire laser emitting 100 fs pulses at 2000 nm with pulse energy of 50 microJ. Temperature gradient induced by infrared laser is introduced to interpret this infrared induced LPV effect. The high position sensitivity reaching 15.3mV/mm and easier fabrication techniques suggests this oxidized film a potential candidate for the novel infrared photodetectors.

A large lateral photovoltaic effect (LPE) has been observed in a Cu2O/Si heterojunction structure when its surface is illuminated by a laser. Moreover, with external bias voltage, the maximal LPE sensitivity can reach up to 1114 mV/mm, which is almost 10 times larger compared with its initial non-biased value of 113 mV/mm. We ascribe this phenomenon mainly to the effect of the increased photo-generated holes caused by the bias. Giant output voltage and high sensitivity suggest the potential of Cu2O nano-films could be used in a wide variety of applications for position-sensitive photodetectors.