Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is an active component from the root and rhizome of Rheum palmatum that has been reported to exhibit antitumor effects through an unknown mechanism. Our study investigated the mechanisms of aloe-emodin-induced cell death in the human lung nonsmall cell carcinoma cell line H460. Aloe-emodin (40 M)-induced apoptosis of H460 cells involves modulation of cAMP-dependent protein kinase, protein kinase C, Bcl-2, caspase-3 and p38 protein expression. Rheum palmatum L. has been used in Chinese medicine for a long time. Previous treatments of diseases with herbs were empirical more than theoretical. Therefore, clarifying the mechanisms of action of the components of herbs may be important for developing their applications. Aloe-emodin, an active component of the root and rhizome of Rheum palmatum L., 1 has been demonstrated to possess anti-tumor activity. [2][3][4] The mechanisms of the aloeemodin-produced anticancer effects, however, remain unknown. The present study served to investigate the mechanisms of aloeemodin-induced apoptosis on human nonsmall cell lung carcinoma cell H460.Apoptosis is a major form of cell death, which involves many factors such as expression and translocation of Bcl-2 family proteins, activation of caspases, expression of protein kinase C (PKC) family, cAMP-dependent protein kinase (PKA) and mitogen-activated protein kinase (MAP kinase) members signal transduction pathways. The Bcl-2 family proteins, such as Bcl-2, Bcl-X L , Bak and Bax, are the best-characterized regulators of apoptosis. 4,5 Caspases, a family of cysteine proteases, play a critical role during apoptosis. There are at least two major mechanisms (one involving caspase-8 and the other involving caspase-9) 6,7 that directly or indirectly activate "effector" caspases such as caspase-3. 8,9 Many investigators have reported that activation of cAMP signaling is involved in apoptosis. 10,11 The role of cAMP in various cell responses is mediated by the cAMP-dependent protein kinase. The dissociation, however, of catalytic subunit from inactive PKA is the marker of the activity of PKA. The present study determined the change of PKAc (PKA catalytic subunit) in aloe-emodininduced apoptosis. PKC represents 11 isozymes that have been implicated in the regulation of apoptosis. 12,13 The contribution of individual PKC isozymes to this process, however, is not well understood. Many reports suggested that the degradation of ␦PKC was directly concerned in apoptosis in all of the PKC isozymes. 13,14 The relationship between activation of caspase and ␦PKC was investigated in many reports. These reports suggest that ␦PKC should lie upstream or downstream of caspase-3. 13,14 We examined the changes of ␦PKC and caspase-3 and the specificity of the PKC-caspase-3 relationship on aloe-emodin-induced apoptosis.The mitogen-activated protein kinase (MAP kinase) members can be grouped into 3 major classes: the extracellular signalregulated protein kinases (ERKs), the c-jun N-terminal kinases (JNKs) ...

The protective effect of magnolol, a component of Magnolia officinalis, against hypoxia-induced cell injury in cortical neuron-astrocyte mixed cultures was examined. Exposure of the cells to chemical hypoxia (0.5 mM KCN) produced morphological changes in neurons but not in astrocytes. KCN induced dose- and time-dependent increases in release of LDH and decreases in viable cell number. Treatment with magnolol (10 and 100 microM) significantly reduced the KCN-induced LDH release in a concentration-dependent manner. A higher concentration (750 microM) magnolol was toxic. Nuclear condensation was not observed in KCN-treated cells, suggesting that chemical hypoxia-induced cell death was via necrosis, rather than via apoptosis. This is the first report demonstrating that magnolol protects neurons against chemical hypoxic damage or necrotic cell death in cortical neuron-astrocyte mixed cultures.

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