Combined Treatment with Coptidis Rhizoma Extract and Arsenic Trioxide Enhanced Apoptosis through Diverse Pathways in H157 Cells
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Coptidis rhizoma (huanglian) is an herb that is widely used in traditional Chinese medicine that has recently been shown to possess anticancer activity. However, the molecular mechanism underlying the anticancer effects of this herb is poorly understood. In this study, we investigated the anticancer activity of a combination of CR extract and arsenic trioxide, as well as the apoptotic pathway associated with its mechanism of action in human lung cancer H157 cells. Combined treatment of H157 cells with CR extract and arsenic trioxide resulted in significant apoptotic death. In addition, combined treatment with CR extract and arsenic trioxide acted in concert to induce a loss of mitochondrial membrane potential (ΔΨ), the release of cytochrome c from mitochondria, and an increase in the expression of pro-apoptotic p53 and Bax protein, which resulted in activation of caspases and apoptosis. CR extract combined with arsenic trioxide also increased the lipid peroxidation, mRNA expression of DR4 and DR5 and caspase-8 activity. These data indicate that combined treatment with CR extract and arsenic trioxide enhanced apoptotic cell death in H157 cells through diverse pathways, including mitochondrial dysfunction and death receptors, particularly DR4 and DR5. Thus, this treatment may be an effective from of chemotherapy.
Abstract
Coptidis rhizoma (huanglian) is an herb that is widely used in traditional Chinese medicine that has recently been shown to possess anticancer activity. However, the molecular mechanism underlying the anticancer effects of this herb is poorly understood. In this study, we investigated the anticancer activity of a combination of CR extract and arsenic trioxide, as well as the apoptotic pathway associated with its mechanism of action in human lung cancer H157 cells. Combined treatment of H157 cells with CR extract and arsenic trioxide resulted in significant apoptotic death. In addition, combined treatment with CR extract and arsenic trioxide acted in concert to induce a loss of mitochondrial membrane potential (ΔΨ), the release of cytochrome c from mitochondria, and an increase in the expression of pro-apoptotic p53 and Bax protein, which resulted in activation of caspases and apoptosis. CR extract combined with arsenic trioxide also increased the lipid peroxidation, mRNA expression of DR4 and DR5 and caspase-8 activity. These data indicate that combined treatment with CR extract and arsenic trioxide enhanced apoptotic cell death in H157 cells through diverse pathways, including mitochondrial dysfunction and death receptors, particularly DR4 and DR5. Thus, this treatment may be an effective from of chemotherapy.
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