Auranofin sensitizes breast cancer cells to paclitaxel chemotherapy by disturbing the cellular redox system.

The intrinsic redox status of cancer cells limits the efficacy of chemotherapeutic drugs. Auranofin, a Food and Drug Administration-approved gold-containing compound, documented with effective pharmacokinetics and safety profiles in humans, has recently been repurposed for anticancer activity. This study examined the paclitaxel-sensitizing effect of auranofin by targeting redox balance in the MDA-MB-231 and MCF-7 breast cancer cell lines. Auranofin treatment depletes the activities of superoxide dismutase, catalase, and glutathione peroxidase and alters the redox ratio in the breast cancer cell lines. Furthermore, it has been noticed that auranofin augmented paclitaxel-mediated cytotoxicity in a concentration-dependent manner in both MDA-MB-231 and MCF-7 cell lines. Moreover, auranofin increased the levels of intracellular reactive oxygen species (observed using 2, 7-diacetyl dichlorofluorescein diacetate staining) and subsequently altered the mitochondrial membrane potential (rhodamine-123 staining) in a concentration-dependent manner. Further, the expression of apoptotic marker p21 was found to be higher in auranofin plus paclitaxel-treated breast cancer cells compared to paclitaxel-alone treatment. Thus, the present results illustrate the chemosensitizing property of auranofin in MDA-MB-231 and MCF-7 breast cancer cell lines via oxidative metabolism. Therefore, auranofin could be considered a chemosensitizing agent during cancer chemotherapy.

Andrographolide protects acute ultraviolet-B radiation-induced photodamages in the mouse skin.

This study evaluates the preventive role of andrographolide (ADP) against ultraviolet-B (UVB) radiation-induced photoaging in the mouse skin. Grouped mice were subjected to UVB irradiation at the dose of 180 mJ/cm2 for ten consecutive days. The ADP (3.6 mg kg/b.wt) was topically administrated 1 h before each UVB-irradiation. We observed that UVB irradiation enhances lipid peroxidative thiobarbituric acid reactive substances (TBARS) and attenuated antioxidant enzyme activities in the mouse skin. Conversely, the ADP pretreatment reversed the lipid peroxidation and restored antioxidant status in the mouse skin. Histological observations clearly show the preventive effect of ADP against UVB-induced dermal tissue damage. Further, ADP slow-down the UVB-mediated expression of inflammatory proteins such as CD34, iNOS, NF-κB COX-2, IL-6, and IL-10 in the mouse skin. Moreover, western blotting studies revealed that ADP prevents UVB exposure-mediated apoptosis markers p53 overexpression in the mouse skin. Thus, ADP protects mouse skin from UVB radiation exposure through impeding inflammation, oxidative stress, and apoptosis.

The Role of 18F-Flortaucipir (AV-1451) in the Diagnosis of Neurodegenerative Disorders.

Tau protein plays a vital role in maintaining the structural and functional integrity of the nervous system; however, hyperphosphorylation or abnormal phosphorylation of tau protein plays an essential role in the pathogenesis of several neurodegenerative disorders. The development of radioligand such as the 18F-flortaucipir (AV-1451) has provided us with the opportunity to assess the underlying tau pathology in various etiologies of dementia. For the purpose of this article, we aimed to evaluate the utility of 18F-AV-1451 in the differential diagnosis of various neurodegenerative disorders. We used PubMed to look for the latest, peer-reviewed, and informative articles. The scope of discussion included the role of 18F-AV-1451 positron emission tomography (PET) to aid in the diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy bodies (DLB), and Parkinson's disease with dementia (PDD). We also discussed if the tau burden identified by neuroimaging correlated well with the clinical severity and identified the various challenges of 18F-AV-1451 PET. We concluded that although the role of 18F-AV-1451 seems promising in the neuroimaging of AD, the benefit appears uncertain when it comes to the non-Alzheimer's tauopathies. More research is required to identify the off-target binding sites of 18F-AV-1451 to determine its clinical utility in the future.