Selective Killing of Cancer Cells by Ashwagandha Leaf Extract and Its Component Withanone Involves ROS Signaling

Ashwagandha is a popular Ayurvedic herb used in Indian traditional home medicine. It has been assigned a variety of health-promoting effects of which the mechanisms remain unknown. We previously reported the selective killing of cancer cells by leaf extract of Ashwagandha (i-Extract) and its purified component Withanone. In the present study, we investigated its mechanism by loss-of-function screening (abrogation of i-Extract induced cancer cell killing) of the cellular targets and gene pathways.Randomized ribozyme library was introduced into cancer cells prior to the treatment with i-Extract. Ribozymes were recovered from cells that survived the i-Extract treatment. Gene targets of the selected ribozymes (as predicted by database search) were analyzed by bioinformatics and pathway analyses. The targets were validated for their role in i-Extract induced selective killing of cancer cells by biochemical and molecular assays. Fifteen gene-targets were identified and were investigated for their role in specific cancer cell killing activity of i-Extract and its two major components (Withaferin A and Withanone) by undertaking the shRNA-mediated gene silencing approach. Bioinformatics on the selected gene-targets revealed the involvement of p53, apoptosis and insulin/IGF signaling pathways linked to the ROS signaling. We examined the involvement of ROS-signaling components (ROS levels, DNA damage, mitochondrial structure and membrane potential) and demonstrate that the selective killing of cancer cells is mediated by induction of oxidative stress.Ashwagandha leaf extract and Withanone cause selective killing of cancer cells by induction of ROS-signaling and hence are potential reagents that could be recruited for ROS-mediated cancer chemotherapy

Ultra‐Sensitive, Self‐powered, CMOS‐Compatible Near‐Infrared Photodetectors for Wide‐Ranging Applications

Publication status: PublishedFunder: Engineering and Physical Sciences Research Council; doi: http://dx.doi.org/10.13039/501100000266AbstractSelf‐powered near‐infrared (NIR) photodetectors are essential for surveillance systems, sensing in IoT electronics, facial recognition, health monitoring, optical communication networks, night vision, and biomedical imaging. However, silicon commercial detectors need external power to operate and cooling to suppress large dark currents. This work demonstrates a new class of CMOS‐compatible self‐powered NIR photodetector based on ferroelectric 5‐nm thick ZrO2 films which do not require cooling and therefore have two key advantages over Si, and at the same time have comparable performance metrics. At room‐temperature, under 940 nm wavelength illumination (1.4 mW cm−2 power density, 10 Hz repetition rate), and without any power applied, fast rise and fall times of ≈2 and 4 µs, respectively, are achieved in Al/Si/SiOx/ZrO2/ITO devices, along with responsivity, detectivity and sensitivity values of up to ≈3.4 A W−1, 1.2 × 1010 Jones and 4.2 × 103, respectively, far exceeding all other emerging self‐powered systems. Furthermore, dual‐band NIR detection is shown for different NIR wavelengths, proof‐of‐concept feasibility being demonstrated for the smart identification of NIR targets. Therefore, it is demonstrated, for the first time, that coupling together the pyroelectric effect, the photovoltaic effect, and the ferroelectric effect is a novel method to significantly enhance the performance of CMOS‐compatible ZrO2‐based self‐powered photodetectors in the NIR region.</jats:p