Melanoma is the most malignant skin cancer. Curcumin has shown to have therapeutic effects when used in the treatment of malignant diseases. However, the precise molecular mechanisms of its action are not fully elucidated. In this research, we hypothesized that reactive oxygen species (ROS) play a key role in curcumin induced DNA damage, apoptosis and cell dead. To test our hypothesis, cytotoxic, genotoxic, apoptotic, ROS generating and mitochondrial membrane potential (MMP) of curcumin on mouse melanoma cancer cells (B16-F10) and fibroblastic normal cells (L-929) were investigated. Our results demonstrated that curcumin decreased cell viability and MMP and, increased DNA damage, apoptosis and ROS levels in both melanoma cancer and normal cells in a dose dependent manner and, these activities were significantly higher in melanoma cells than in normal cells with higher concentrations. There were positive strong relationships between DNA damage, apoptosis, cytotoxicity and ROS generation and MMP levels in curcumin treated melanoma and normal cells. In summary, this in vitro study provide clear evidence that curcumin induced DNA damage, apoptosis and cytotoxicity via its pro-oxidant activity in a dose dependent manner in both cancer and normal cells and these activities were higher in cancer cells than those of normal cells.

Gastric cancer (GC) is the most common cause of morbidity and mortality because of cancer. Medicinal plants containing polyphenolic compounds have gained importance in anticancer treatment. In this context, carvacrol is a main component of many plants in the family Lamiaceae that are frequently used in folk medicine and a good candidate to investigate for GC treatment. The present study aimed to explore the cytotoxic, genotoxic, apoptotic, and reactive oxygen species (ROS)-generating effects of carvacrol on gastric adenocarcinoma in vitro. For these purposes, human gastric adenocarcinoma (AGS) cells were used and analyzed after 24 h of exposure to carvacrol with different concentrations. The cytotoxicity, ROS generation, glutathione (GSH) level, and genotoxicity were investigated by the ATP cell viability assay, 2′,7′-dichlorodihydrofluorescein-diacetate assay, GSH/GSSG-Glo assay, and comet assay, respectively. Apoptosis induction was detected by acridine orange/ethidium bromide staining and western blotting at below the half-maximal growth inhibitory concentration value. Carvacrol showed cytotoxic, genotoxic, apoptotic, ROS generating, and GSH-reducing effects on AGS cells in a dose-dependent manner. There was a close negative relationship between cell viability and ROS level. Carvacrol inhibited the proliferation of AGS cells, suggesting that it could be a novel and strong anticancer agent against the human gastric adenocarcinoma. These results support the interest of natural diet components in the development of therapeutic products for diseases.

The aim of this study was to evaluate the amount of leached residual monomers from self-adhesive resin cements and evaluate their toxicity in-vitro. A total of 60 disk-shaped specimens (5 mm in diameter and 0.5 mm in thickness) were prepared from each cement (RelyX U200, SpeedCEM, G-Cem) (n=20). Specimens were immersed in artificial saliva and the amount of released monomers [urethane dimethacrylate (UDMA) and triethyleneglycol dimethacrylate (TEGDMA)] was identified. Then, the cytotoxicity and genotoxicity effect on cells were evaluated using the defined amounts of released monomers from cements. The highest monomer release was detected in G-Cem (p<0.05). The highest cytotoxicity value was identified from SpeedCEM (p<0.01) and the highest genotoxicity values were calculated from RelyX U200 (p<0.05). Released UDMA and TEGDMA from self-adhesive resin cements induced cytotoxicity and genotoxicity effect on cells.

Carbonic anhydrase IX (CAIX) is a hypoxia-related protein that plays a role in proliferation in solid tumours. However, how CAIX increases proliferation and metastasis in solid tumours is unclear. The objective of this study was to investigate how a synthetic CAIX inhibitor triggers apoptosis in the HeLa cell line. The intracellular effects of CAIX inhibition were determined with AO/EB, AnnexinV-PI, and γ-H2AX staining; measurements of intracellular pH (pHi), reactive oxygen species (ROS), and mitochondrial membrane potential (MMP); and analyses of cell cycle, apoptotic, and autophagic modulator gene expression (Bax, Bcl-2, caspase-3, caspase-8, caspase-9, caspase-12, Beclin, and LC3), caspase protein level (pro-caspase 3 and cleaved caspase-3, -8, -9), cleaved PARP activation, and CAIX protein level. Sulphonamide CAIX inhibitor E showed the lowest IC₅₀ and the highest selectivity index in CAIX-positive HeLa cells. CAIX inhibition changed the morphology of HeLa cells and increased the ratio of apoptotic cells, dramatically disturbing the homeostasis of intracellular pHi, MMP and ROS levels. All these phenomena consequent to CA IX inhibition triggered apoptosis and autophagy in HeLa cells. Taken together, these results further endorse the previous findings that CAIX inhibitors represent an important therapeutic strategy, which is worth pursuing in different cancer types, considering that presently only one sulphonamide inhibitor, SLC-0111, has arrived in Phase Ib/II clinical trials as an antitumour/antimetastatic drug.