Breast cancer is the second leading cause of death among women globally. The existing treatment options for breast cancer are largely associated with severe toxicities, and lower efficacies. Therefore, there is an urgent need for the development of non-toxic effective drugs against breast cancer. For this purpose, drug repositioning strategy was used to evaluate the anti-cancer potential of a library of heterocyclic drugs. The major advantage of drug repurposing is that the pharmacokinetic, pharmacodynamic, and toxicity profiles of drugs are well documented. In the current study, we screened 97 drugs of different chemical classes, and among them aripiprazole, an antipsychotic drug, was found to be sufficiently active against breast cancer cell line MCF-7. Aripiprazole showed a cytotoxicity (IC 50 = 12.1 ± 0.40 μM) to MCF-7 cells, comparable to the standard anticancer drug doxorubicin (IC 50 = 1.25 ± 0.34 μM). Aripiprazole was also found to be active against other cancer cell lines, including MDA-MB-231 (IC 50 = 19.83 ± 0.27 μM), AU565 (IC 50 = 18.02 ± 0.44 μM), and BT-474 (IC 50 = 36.42 ± 0.12 μM). Aripiprazole significantly inhibited the cell cycle progression at subG 0 G 1 phase, and enhanced apoptosis in MCF-7 breast cancer cells. The drug was also able to significantly increase the nuclear condensation, and modulated the expression of certain genes involved in breast cancer, such as caspases 3, and 9, BAK-1, C-MYC, BCL2L1, BCL-10, and BCL-2. Further studies are needed to explore the effect of aripiprazole on intrinsic and extrinsic pathways of apoptosis in cancer cells.

Zerumbone is a well-known compound having anti-cancer, anti-ulcer, anti-inflammatory and anti-hyperglycemic effects. During its use for the disease treatment, the membrane of erythrocyte can be affected by consumption of this bioactive compound. The current study was the first report of investigation of the hemolytic activities on human erythrocytes and cytotoxic profile of zerumbone. The toxicity of zerumbone on human erythrocytes was determined by in vitro hemolytic assay. Brine shrimp lethality assay was used to evaluate the cytotoxic effect of zerumbone at concentrations 10, 100 and 1000 μg/mL. The human erythrocyte test showed no significant toxicity at low concentrations, whereas hemolytic effect was amplified up to 17.5 % at the highest concentration. The half lethal concentration (LC50) value of zerumbone against brine shrimp was less than 1000 µg /mL (LC50=190 µg/ml) showing the significant toxic nature of this compound. These results provide a baseline in terms of the toxicity of therapeutic formulations from this compound to membrane erythrocytes with a great attention to the highest concentrations, which paves promise for drug development.

Zerumbone (ZER), a natural compound has been extracted from Zingiber zerumbet with known pharmacological activities. The aim was to determine the anti-human Burkitt's lymphoma (Raji) cell effect of ZER. The 3-(4,5-dimethylthiazol-2-yl)-2,5,diphenyltetrazolium bromide (MTT) assay was used to determine cytotoxic effect while the Annexin-V-fluorescein isothiocyanate/propidium iodide-PI flow cytometric assays was used to determine apoptotic effect of ZER on the human Burkitt's lymphoma (Raji) cell (ATCC CCL-86) cell line. The expressions of Bax, Bcl-2, and c-Myc genes were determined via real-time PCR. ZER suppressed the proliferation of Raji cells with a 48 h IC50 value of 5.1 μg/mL. Treated Raji cells also underwent late apoptosis especially after treatment with 100 μg/mL ZER. The apoptotic effect of ZER is associated with increase in Bax and decrease in Bcl-2 and c-Myc gene expressions. These results suggest that ZER inhibited the proliferation of Raji cells through the modification of apoptosis-related gene expressions. Therefore, ZER has potential as a candidate for the treatment of Burkitt's lymphoma.

Context: Clausena excavata Burm. f is a plant used in folklore medicine for the treatment of various ailments in South East Asia. The plant parts contain chemical components that are cytotoxic to many cancer cells. Objective: The study investigated the cytotoxic effects of ethyl acetate, methanol and chloroform C. excavata leaf extracts on the nonsmall-lung cancer, NCI-H460, cell line. Methods: Based on the 3-(4,5-dimethylthiazol-2-yl)-2,5,-diphenyltetrazolium bromide (MTT) assay, among extracts, ethyl acetate C. excavata leaf extract (EACE) was the most potent anti-NCI-H460 cells, with IC 50 value of 47.1 ± 6.1 μg/ml. The effects of EACE on NCI-H460 cells were also determined by clonogenic, 4', 6-diamidino-2-phenylindole (DAPI), and annexin-V-fluorescein isothiocyanate/ propidium iodide-PI flow cytometric assays. Reactive oxygen species (ROS) production and apoptotic gene expressions was determined via flow cytometry and real-time quantitative PCR, respectively. Results: EACE-treated NCI-H460 cells after 48 h underwent apoptosis as evident by loss of cell viability, cell shrinkage, and chromatin condensation. The results also showed EACE mediated increase in ROS production by the NCI-H460 cells. After 48 h treatment, EACE increased the pro-apoptotic BAX and decreased the anti-apoptotic Bcl-2, Survivin and c-Myc gene expressions. Conclusions: EACE is a potential anti-lung cancer by increasing cancer cell ROS production and apoptosis.