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Demethoxycurcumin (DMC) is a key component of Chinese medicine (Turmeric) and has been proven effective in killing various cancer cells. Its role in inducing cytotoxic effects in many cancer cells has been reported, but its role regarding DNA damage on lung cancer cells has not been studied in detail. In the present study, we demonstrated DMC-induced DNA damage and condensation in NCI-H460 cells by using the Comet assay and DAPI staining examinations, respectively. Western blotting indicated that DMC suppressed the protein levels associated with DNA damage and repair, such as 14-3-3σ (an important checkpoint keeper of DNA damage response), DNA repair proteins breast cancer 1, early onset (BRCA1), O6-methylguanine-DNA methyltransferase (MGMT), mediator of DNA damage checkpoint 1 (MDC1), and p53 (tumor suppressor protein). DMC activated phosphorylated p53 and p-H2A.X (phospho Ser140) in NCI-H460 cells. Furthermore, we used confocal laser systems microscopy to examine the protein translocation. The results showed that DMC promotes the translocation of p-p53 and p-H2A.X from the cytosol to the nuclei in NCI-H460 cells. Taken together, DMC induced DNA damage and affected DNA repair proteins in NCI-H460 cells in vitro., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Gallic acid (GA), a phenolic compound naturally present in plants, used as an antioxidant additive in food and in the pharmaceutical industry, may have cancer chemopreventive properties. In the present study, we investigated whether GA induced DNA damage and affected DNA repair-associated protein expression in human oral cancer SCC-4 cells. Flow cytometry assays were used to measure total viable cells and results indicated that GA decreased viable cells dose-dependently. The comet assay and 4',6-Diamidino-2-phenylindole dihydrochloride (DAPI) staining were used to measure DNA damage, as well as condensation and it was shown that GA induced DNA damage (comet tail) and DNA condensation in a dose-dependent manner. DNA gel electrophoresis was used to examine DNA fragmentation and we found that GA induced DNA ladder (fragmentation). Using western blotting it was shown that GA inhibited the protein expressions of MDC1, O(6)-methylguanine-DNA methyltransferase (MGMT), p-H2A.X, p53, DNA-dependent serine/threonine protein kinase (DNA-PK) and 14-3-3 proteins sigma (14-3-3σ) but increased p-p53, phosphate-ataxia-telangiectasia (p-H2A.X) and ataxia telangiectasia mutated and Rad3-related (p-ATR), phosphate-ataxia telangiectasia mutated (p-ATM) and breast cancer susceptibility protein 1 (BRCA1) in a 24-h treatment. The protein translocation was examined by confocal laser microscopy and results indicated that GA increased the levels of p-H2A.X, MDC1 and p-p53 in SCC-4 cells. In conclusion, we found that GA-induced cell death may proceed through the induced DNA damage and suppressed DNA repair-associated protein expression in SCC-4 cells., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Cancer metastasis is the major cause of cancer patient death. Melanoma is a highly important metastasis in human cancer. Cantharidin (CTD), identified as an active component of natural mylabris (Mylabris phalerata Pallas), induces apoptosis in many human cancer cells. In the present study, we investigated the anti-metastasis effects of CTD in human melanoma cancer A375.S2 cells. Flow cytometry was used to measure CTD-induced cytotoxic effects in A375.S2 cells. Wound healing assay indicated that CTD suppressed the migration of A375.S2 cells in a dose-dependent manner. The Matrigel Transwell Assay was used for cell migration and invasion examination and the results showed that CTD inhibited both. Gelatin zymography was used to investigate the activities of MMP-2/9 and the results indicated that CTD inhibited the enzymatic activities of MMP-2/9 in A375.S2 cells. The protein expression of A375.S2 cells following incubation with CTD was examined by western blotting and the results showed that CTD decreased the expression of ERK1/2, PI3K, FAK, MMP-2, -9, COX-2, NF-κB p65, TIMP 1, TIMP 2, VEFG, uPA, Rho A, GRB2, ROCK-1 and Ras, but increased the expressions of p38, JNK, p-c-jun and PKC. Based on those observations, we suggest that CTD may be used as a novel anti-cancer metastasis agent of human melanoma cancer in the future., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Phenethyl isothiocyanate (PEITC), one of many compounds found in cruciferous vegetables, has been reported as a potential anticancer agent. In earlier studies, PEITC was shown to inhibit cell growth and induction of apoptosis in many cancer cell lines. However, no report has shown whether PEITC can induce apoptosis in human prostate cancer cells. Herein, we aimed to determine whether PEITC has anticancer activity in DU 145 human prostate cancer cells. As a result, we found that PEITC induced a dose-dependent decrease in cell viability through induction of cell apoptosis and cell cycle arrest in the G(2)/M phase of DU 145 cells. PEITC induced morphological changes and DNA damage in DU 145 cells. The induction of G(2)/M phase arrest was mediated by the increase of p53 and WEE1 and it reduced the level of CDC25C protein. The induction of apoptosis was mediated by the activation of caspase-8-, caspase-9- and caspase-3-depedent pathways. Results also showed that PEITC caused mitochondrial dysfunction, increasing the release of cytochrome c and Endo G from mitochondria, and led cell apoptosis through a mitochondria-dependent signaling pathway. This study showed that PEITC might exhibit anticancer activity and become a potent agent for human prostate cancer cells in the future.