Here, we report the therapeutic potential of a natural quinazoline derivative (2-chloro-6-phenyl-8H-quinazolino[4,3-b]quinazolin-8-one) isolated from marine sponge Hyrtios erectus against human breast cancer. The cytotoxicity of the compound was investigated on a human breast carcinoma cell line (MCF-7). Antiproliferative activity of the compound was estimated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MTT assay showed significant inhibition of MCF-7 cells viability with the IC50 value of 13.04 ± 1.03 µg/mL after 48 h. The compound induced down-regulation of anti-apoptotic Bcl-2 protein and increase in the pro-apoptotic Bax/Bcl-2 ratio in MCF-7 cells. The compound activated the expression of Caspases-9 and stimulated downstream signal transducer Caspase-7. In addition, Caspase-8 showed remarkable up-regulation in MCF-7 cells treated with the compound. Moreover, the compound was found to promote oxidative stress in MCF-7 cells that led to cell death. In conclusion, the compound could induce apoptosis of breast carcinoma cells via a mechanism that involves ROS production and either extrinsic or intrinsic apoptosis pathways. The systemic toxic potential of the compound was evaluated in an in vivo mouse model, and it was found non-toxic to the major organs.

The burrowing mite Sarcoptes scabiei causes scabies in humans or mange in animals. It infests a wide range of mammalian species including livestock, companion animals, wild animals, and humans. Differential diagnosis of Sarcoptes varieties is key for epidemiological studies and for formulation of an eradication program. Host-parasite interaction at the systemic level is very important to understand the pathogenicity of the mite. This communication deals with the preliminary report on the genetic characterization of S. scabiei from India. Moreover, the effect of S. scabiei infestation on host physiology with special emphasis on serum biochemical parameters, lipid profile, oxidant/antioxidant balance, stress parameters, and immune responses were evaluated in a porcine model. Cytochrome C oxidase 1 and voltage-sensitive sodium channel based phylogenetic study could distinguish human and animals isolates but could not distinguish host or geographical specific isolates belonging to animal origin. An absence of host-specific cluster among animal isolates argues against the hypothesis of delineating S. scabiei as per host origin. Elevated levels of markers of liver function such as albumin, AST, ALT, ALP, and LDH in infested animals indicated impaired liver function in infested animals. S. scabiei infestation induced atherogenic dyslipidemia indicated by elevated levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides, and a decreased level of high-density lipoprotein cholesterol. Oxidative stress in infested animals was indicated by a high level of nitric oxide and serum MDA as oxidative stress markers and low antioxidant capacity. S. scabiei triggered stress response and elevated levels of serum cortisol and heat shock proteins were recorded in infested animals. S. scabiei infestation increased the serum concentration of immunoglobulins and was associated with up-regulation of IL-2, IFN-γ, IL-1β, and IL-4 indicating both Th1 and Th2 response. The results of the study will be helpful for a better understanding of host-parasite interaction at the systemic level in crusted scabies in pigs.