Synergistic antitumor effect of β-elemene and etoposide is mediated via induction of cell apoptosis and cell cycle arrest in non-small cell lung carcinoma cells.
ABSTRACT β-Elemene, an anticancer agent, was isolated from the traditional Chinese medicine plant, curcuma aromatica. In this study, we investigated the synergistic antitumor effect of β-elemene and etoposide phosphate (VP-16) in A549 non-small cell lung carcinoma cells. The cells were treated with β-elemene (20 or 50 µg/ml), VP-16 (15 µg/ml) or the combination of both for 24 h. Compared to the treatment with β-elemene or VP-16 alone, an increased antitumor activity was observed with the combination of both, which was mediated by the cleavage of PARP, the up-regulation of Bax, p53 and p21, and the suppression of cyclin D1. These results suggest that the combination of β-elemene and VP-16 may be a promising therapeutic option for lung cancer.
- SourceAvailable from: Christos K Kontos[show abstract] [hide abstract]
ABSTRACT: Classical chemotherapeutic agents such as mitotic inhibitors (spindle poisons), alkylating agents, antimetabolites, topoisomerase inhibitors, and anthracenediones (anthracyclines) inhibit DNA synthesis and mitosis, thereby killing or impeding the proliferation of rapidly dividing cells. During the last decade, targeted therapy has gained advantage over conventional treatment regimens, as it is more effective against cancer and also much less harmful to normal cells, thus minimizing the side-effects of chemotherapy. This type of treatment blocks the proliferation of cancer cells by inhibiting the function of specific targeted molecules needed for tumor growth and metastasis. Targeted therapy agents include monoclonal antibodies and small-molecule inhibitors, which most commonly target receptor and/or non-receptor tyrosine kinases. Most members of the BCL2 apoptosis-related family regulate cellular fate as a response to antineoplastic agents. Modulations at the mRNA and protein levels of these genes are usually associated with sensitivity or resistance of various types of cancer cells to chemotherapeutic drugs. Moreover, alterations in expression of BCL2-family members, induced by anticancer drug treatment, can trigger or simply facilitate apoptosis. In this review, we summarize information about changes in apoptosis-related gene expression caused directly or indirectly by antineoplastic agents, as well as about the impact of BCL2-family members on the chemosensitivity or chemoresistance of cancer cells.Anti-cancer agents in medicinal chemistry 06/2013;
- [show abstract] [hide abstract]
ABSTRACT: As a tumor suppressor protein, p53 plays a crucial role in the cell cycle and in cancer prevention. Almost 50 percent of all human malignant tumors are closely related to a deletion or mutation in p53. The activity of p53 is inhibited by over-active celluar antagonists, especially by the over-expression of the negative regulators MDM2 and MDMX. Protein-protein interactions, or post-translational modifications of the C-terminal negative regulatory domain of p53, also regulate its tumor suppressor activity. Restoration of p53 function through peptide and small molecular inhibitors has become a promising strategy for novel anti-cancer drug design and development. Molecular dynamics simulations have been extensively applied to investigate the conformation changes of p53 induced by protein-protein interactions and protein-ligand interactions, including peptide and small molecular inhibitors. This review focuses on the latest MD simulation research, to provide an overview of the current understanding of interactions between p53 and its partners at an atomic level.International Journal of Molecular Sciences 01/2012; 13(8):9709-40. · 2.46 Impact Factor