Antimicrobial and antitumor properties of anuran peptide temporin-SHf induce apoptosis in A549 lung cancer cells.

Temporin-SHf is a linear, ultra-short, hydrophobic, α-helix, and phe-rich cationic antimicrobial peptide. The antitumor activities and mechanism of temporin-SHf-induced cancer cell death are unknown. The temporin-SHf was synthesized by solid-phase Fmoc chemistry and antimicrobial and antitumor activities were investigated. Temporin-SHf was microbiocidal, non-hemolytic, and cytotoxic to human cancer cells but not to non-tumorigenic cells. It affected the cancer cells' lysosomal integrity and caused cell membrane damage. The temporin-SHf inhibited A549 cancer cell proliferation and migration. It is anti-angiogenic and causes cancer cell death through apoptosis. The molecular mechanism of action of temporin-SHf confirmed that it kills cancer cells by triggering caspase-dependent apoptosis through an intrinsic mitochondrial pathway. Owing to its short length and broad spectrum of antitumor activity, temporin-SHf is a promising candidate for developing a new class of anticancer drugs.

Jatamansinol from Nardostachys jatamansi Ameliorates Tau-Induced Neurotoxicity in Drosophila Alzheimer's Disease Model.

Nardostachys jatamansi has long been used to prepare Medhya Rasayana in traditional Indian Ayurveda medicine to treat neurological disorders and enhance memory. Jatamansinol from the N. jatamansi against Alzheimer's disease (AD) showed that it could be a multitargeted drug against AD. Drosophila is an ideal model organism for studying a progressive age-related neurodegenerative disease such as AD since its neuronal organizations and functioning are highly similar to that of humans. The current study investigates the neuroprotective properties of jatamansinol against Tau-induced neurotoxicity in the AD Drosophila model. Results indicate jatamansinol is not an antifeedant for larva and adult Drosophila. Lifespan, locomotor activity, learning and memory, Tau protein expression level, eye degeneration, oxidative stress level, and cholinesterase activities were analyzed in 10, 20, and 30-day-old control (wild type), and tauopathy flies reared on jatamansinol supplemented food or regular food without jatamansinol supplementation. Jatamansinol treatment significantly extends the lifespan, improves locomotor activity, enhances learning and memory, and reduces Tau protein levels in tauopathy flies. It boosts the antioxidant enzyme activities, prevents Tau-induced oxidative stress, ameliorates eye degeneration, and inhibits cholinesterase activities in Tau-induced AD model. This study provides the first evidence that jatamansinol protects against Tau's neurotoxic effect in the AD Drosophila model, and it can be a potential therapeutic drug candidate for AD.

Antitumor activity of Tigerinin-1: Necroptosis mediates toxicity in A549 cells.

BACKGROUND: Tigerinins are antimicrobial peptides (AMPs) derived from the skin secretions of the Indian bullfrog Hoplobatrachus tigerinus. METHODS: Tigerinin-1 (FCTMIPIPRCY-Am) peptide was synthesized by solid-phase Fmoc chemistry and investigated its antitumor activities. RESULTS: Tigerinin-1 was cytotoxic to human cancer cells. It causes necrosis by damaging the cell membrane and loss of lysosome integrity. Tigerinin-1triggers the expression of necroptosis pathway proteins. It generates reactive oxygen species (ROS) and induces oxidative stress-mediated genotoxicity. Tigerinin-1 inhibits cancer cell proliferation, reduces neovascularization, and down-regulates the vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and fibroblast growth factor (FGF) genes. CONCLUSIONS: Tigerinin-1 exhibited its potent antitumor properties in this study. GENERAL SIGNIFICANCE: Tigerinin-1 can be beneficial for developing novel therapeutics for cancer.

Lead (Pb)-induced oxidative stress mediates sex-specific autistic-like behaviour in Drosophila melanogaster.

Autism spectrum disorder (ASD) is a highly prevalent neurodevelopmental disorder characterised by three main behavioural symptoms: abnormal social interaction, verbal and non-verbal communication impairments, and repetitive and restricted activities or interests. Even though the exact aetiology of ASD remains unknown, studies have shown a link between genetics and environmental pollutants. Heavy metal lead (Pb), the environmental pollutant, is associated with ASD. Pb may also exhibit sex-specific ASD behaviour, as has been demonstrated in the global human populations. Drosophila melanogaster as a model has been used in the present study to understand the involvement of Pb-induced oxidative stress in developing ASD behaviour. The larval feeding technique has been employed to administer different Pb concentrations (0.2-0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) antioxidants overexpressed or knockdown flies. Adult Drosophila (5-day old) were used for Pb content, biochemical, and behavioural analysis.Pb accumulated in the Drosophila brain induces oxidative stress and exhibited a human autistic-like behaviour such as reduced climbing, increased grooming, increased social spacing, and decreased learning and memory in a sex-specific manner.Pb-induced autistic-like behaviour was intensified in Sod or Cat-knockdown flies, whereas Sod or Cat-overexpressed flies overcome that behavioural alterations. These results unequivocally proved that Pb-induced oxidative stress causes ASD behaviour of humans in Drosophila. Thus, Drosophila is used as a model organism to analyse ASD-like human behaviour and underlines the importance of using antioxidant therapy in alleviating ASD symptoms in children.

Lead (Pb) induced Oxidative Stress as a Mechanism to Cause Neurotoxicity in Drosophila melanogaster.

The widespread use of lead (Pb) has caused global contamination, inevitable human exposure, and public health problems. Pb neurotoxicity has been linked to various human diseases, but its associated mechanism causing neurotoxicity is unknown. Drosophila melanogaster as a model organism has been used to study the mechanism involved in Pb-caused neurotoxicity and the potential role of antioxidants in ameliorating its harmful effects. The larval feeding technique was adopted to administer different concentrations of Pb (0.2-0.8 mM) to Oregon-R (ORR), superoxide dismutase (Sod), or catalase (Cat) overexpressing, and Sod or Cat knockdown flies to analyse Pb load, oxidative stress components, DNA damage, apoptosis and vacuolation in the brain. The results revealed that Pb accumulation in the Drosophila brain induces oxidative stress by generating reactive oxygen species (ROS) and lipid peroxidation (LPO), depleting antioxidant enzymes. Molecular docking studies have evidenced it. Pb directly binds to antioxidants and major grooves of DNA, leading to DNA damage. Increased DNA damage, apoptosis, vacuolation in brains of Pb-treated ORR, Sod, or Cat knockdown flies; and on the contrary, reduced oxidative DNA damage, apoptosis, and vacuolation in brains of Pb treated Sod or Cat overexpressed flies put forward that oxidative stress is the mechanism in Pb caused neurotoxicity.

Hyperthermia enhances methyl methanesulfonate-induced adaptive response in meiotic cells of grasshopper Poecilocerus pictus.

To understand the role of hyperthermia (HT) in adaptive response, methyl methanesulfonate (MMS) adapted meiotic cells of Poecilocerus pictus were used. Poecilocerus pictus were treated with conditioning (L) or challenging (H) dose of MMS and 2-h time lag (TL) between these doses (L-2h-H) (combined) was employed. Different treatment schedules were used to analyse the influence of HT on MMS-induced adaptive response namely pre; inter; post-treatment and cross-adaptation. After each treatment schedules, chromosomal anomalies were analysed. The frequencies of chromosomal anomalies induced by conditioning and challenging doses of MMS were significantly higher (P < 0.0001) compared to that of the control or HT groups. The combined treatments resulted in significant reduction of chromosomal anomalies compared to additive effect of MMS (P < 0.0001). The pre, inter, post and cross-adaptation treatments with HT reduced the frequencies of chromosomal anomalies compared to the challenge and combined treatments with MMS. There is a protection against MMS-induced chromosomal anomalies by HT in in vivo P.pictus. This is the first report to demonstrate that HT enhances the MMS-induced adaptive response in in vivo meiotic cells.