Abstract. The present study demonstrates the mechanism of 2 flavonol glycosides, hyperoside and rutin, in the induction of apoptosis in HT-29 human colon cancer cells through the bioactivity-guided fractionation and isolation method. The chemical structure of hyperoside and rutin, isolated from the roots of Nelumbo nucifera, were established using extensive 1-and 2-dimensional nuclear magnetic resonance experiments and absolute high resolution fast-atom bombardment mass spectrometry, ultraviolet-visible and Fourier transform infrared spectroscopy spectral analytical methods. The treatment of HT-29 colon cancer cells with hyperoside and rutin significantly decreased cell viability in a dose-dependent manner. The concomitant activation of the mitochondria-dependent apoptotic pathway of hyperoside and rutin occurred via modulation of Bcl-2-associated X protein and B-cell lymphoma 2 expression, resulting in the activation of cleaved caspases-3, -8 and -9 and cleaved poly-(ADP-ribose) polymerase. The findings of the present study indicate that hyperoside and rutin induce apoptosis in HT-29 human colon cancer cells, and that this phenomenon is mediated via the death receptor-mediated and mitochondria-mediated apoptotic pathways. These results suggest that hyperoside and rutin may be useful in the development of a colon cancer therapy protocol.
Abstract. The present study was performed to determine the effect of Moringa oleifera fruit extract on the apoptosis of human melanoma A2058 cells. A2058 cells were treated for 72 h with Moringa oleifera fruit extract at 50-100 µg/ml, and cell viability with apoptotic changes was examined. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) was examined. It was revealed that Moringa oleifera fruit extract significantly inhibited the cell viability and promoted apoptosis of A2058 cells in a concentration-dependent manner. Moringa oleifera fruit extract-treated A2058 cells exhibited increased activities of cleaved caspase-9 and caspase-3. It also caused an enhancement of MAPK phosphorylation and ROS production. The pro-apoptotic activity of Moringa oleifera fruit extract was significantly reversed by pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125, extracellular-signal-regulated kinase (ERK) inhibitor PD98058 or ROS inhibitor N-acetyl-L-cysteine. Taken together, Moringa oleifera fruit extract is effective in inducing mitochondrial apoptosis of A2058 cells, which is mediated through induction of ROS formation, and JNK and ERK activation. Moringa oleifera fruit extract may thus have therapeutic benefits for human melanoma A2058 cells.
− Moringa oleifera Lam (M. oleifera, Moringaceae) is a tree of the Moringaceae family that can reach a height of between 5 and 10 m. The current paper presents cytotoxic effect of M. oleifera fruits and its flavonoids 1 and 2. The viability of HCT116 human colon cancer cells were 38.5% reduced by 150 µg/mL of ethanolic extracts in a concentration-dependent manner; in addition, we observed the apoptotic features of cell shrinkage and decreased cell size. Bcl-2 family proteins were regulated as determined by Western blotting analysis, suggesting that M. oleifera fruits and their flavonoids 1 and 2 induced apoptosis through an intrinsic pathway. Based on our findings, 70% ethanolic extracts of M. oleifera fruits and flavonoids 1 and 2 might be useful as cytotoxic agents in colorectal cancer therapy.
The present study was designed to investigate the molecular mechanisms of bioactive components against mild oxidative stress in human keratinocytes (HaCaTs). Solvent extraction and fractionation of the rhizomes of Zingiber officinale resulted in the isolation of [10]-gingerol. At concentrations of 1, 3, and 5 µM [10]-gingerol dose-dependently increased HO-1 (heme oxygenase-1) mRNA and protein levels, with a significant effect at 5 µM. This augmentation of HO-1 by [10]-gingerol was attributed to the upregulation of Nrf2 (nuclear factor erythroid 2-related factor 2), which markedly reduced the cytoplasmic stability of Keap1 (kelch-like ECH-associated protein 1). Furthermore, our findings indicate that the upregulation of HO-1 by [10]-gingerol increased resistance to mild oxidative stress, suggesting that [10]-gingerol might enhance the activities of antioxidant enzymes by stimulating Nrf2. Our experimental findings indicate that the mild attenuating effect of [10]-gingerol against oxidative stress involves the ERK/Nrf2/HO-1 signaling pathway.
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