Cacalol, a natural sesquiterpene, induces apoptosis in breast cancer cells by modulating Akt-SREBP-FAS signaling pathway
ABSTRACT We previously isolated cacalol as a free radical-scavenging compound from Cacalia delphiniifolia which is a traditional Asian herbal plant and is believed to have medicinal effects on cancer. In this report, we demonstrated that cacalol has strong anti-proliferation effect on breast cancer cells and induces apoptosis by activating a pro-apoptotic pathway. We also found that a combination of cacalol and other chemotherapeutic drugs (Taxol and cyclophosphamide) synergistically induced apoptosis and partially overcame chemo-resistance. To further gain a mechanistic insight, we tested a potential inhibitory effect of cacalol on fatty acid synthase gene (FAS) in breast cancer cells, and found that cacalol significantly modulated the expression of the FAS gene, which resulted in apoptosis through activation of DAPK2 and caspase 3. We have also shown that cacalol significantly suppressed the Akt-sterol regulatory element-binding proteins (SREBP) signaling pathway and concomitant transcriptional activation of FAS. In a xenograft model of nude mouse, when cacalol was administered intraperitoneally, tumor growth was significantly suppressed. Importantly, oral administration of cacalol before implanting tumors showed significant preventive effect on tumor growth in the same animal model. Furthermore, the treatment of mice with a combination of low dose of Taxol and cacalol significantly suppressed the tumor growth. Taken together, our results indicate that cacalol induces apoptosis in breast cancer cells and impairs mammary tumor growth in vivo by blocking the expression of the FAS gene through modulation of Akt-SREBP pathway, suggesting that cacalol has potential utility as a chemopreventive and chemotherapeutic agent for breast cancer.
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ABSTRACT: Based on a common belief, herbal medicine with the least possible side effects should be the center of attention in cancer care; however, in many cases they have not been properly studied with reliable clinical trials in human subjects. In this review, it was attempted to identify the available evidence on the use and clinical effects of herbs in cancer care. The research consists of two major parts including immunomodulator and chemopreventive herbal compounds whose mechanism, biological response, anticancer element of extract and related benefits were completely studied. Also, the safety of herbal anticancer compounds was discussed. Although the use of herbal medicines in treating cancer shows less chemotherapy-induced, toxicity, more researches are required to reach their full therapeutic potentials.04/2012; 5(3).
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ABSTRACT: Photodynamic therapy (PDT) is an emerging cancer treatment based on the production of singlet oxygen (1O2) upon illumination of a photosensitizer in the presence of oxygen. Antioxidants are primarily reducing agents prone to scavenge reactive species in one way or another. Cacalol (C) and cacalol acetate (CA) were examined and compared regarding to their capacity to produce singlet oxygen and as scavengers of free radicals. Their role as singlet oxygen photoproducers under UV-vis light irradiation was examined by electron paramagnetic resonance (EPR) using 2,2,6,6-tetramethyl-piperidine (TEMP) as spin-trapping material. The quantum yield to produce 1O2 was found to be 0.4 ± 0.05 for CA and 0.13 ± 0.05 for C. Their properties as scavengers of hydroxyl (˙OH), nitrogen-centered (2,2-diphenyl-1-picryhydrazyl radical, DPPH˙) and organic radicals (R˙ and ROO˙) were evaluated using EPR and the thiobarbituric reactive substances (TBARS) method. C and CA differed in their abilities to trap DPPH˙. By contrast, both compounds showed similar activity to trap ˙OH, R˙ and ROO˙. A relationship between the redox potentials of the compounds and their activity as scavengers of DPPH˙ was observed. The producing/inhibiting properties showed by C and CA make them interesting options for new therapeutic applications to treat tumors and other diseases.RSC Advances 01/2014; 4(3):1371. DOI:10.1039/c3ra42848f · 3.71 Impact Factor
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ABSTRACT: BACKGROUND: The aims of this study were to evaluate the apoptotic activities and molecular mechanisms of methanol extracts of Dianthus chinensis (MEDC) and Acalypha australis L. (MEAL) in human oral cancer cells. METHODS: The apoptotic effects and related molecular mechanisms of MEDC and MEAL on oral cancer cells were evaluated using MTS assay, DAPI staining, immunostaining, Western blotting, and reverse transcriptase-polymerase chain reaction. RESULTS: Sp1 was overexpressed in oral tumor tissues compared with normal oral mucosa. Downregulation of Sp1 inhibited the growth of SCC-15 and YD-15 oral cancer cells. MEDC and MEAL inhibited cell growth and induced apoptosis in both cell lines by decreasing the expression of Sp1. In addition, treatment of cells with MEDC and MEAL decreased Mcl-1 expression, which is a downstream target of Sp1. CONCLUSION: Our results indicate that MEDC and MEAL are bioactive natural products that can potentially induce apoptosis of tumor cells that overexpress the Sp1 protein. © 2012 Wiley Periodicals, Inc. Head Neck, 2012.Head & Neck 07/2013; 35(7). DOI:10.1002/hed.23072 · 3.01 Impact Factor