Novel purine ribonucleoside analogues (9-13) containing a 4-substituted piperazine in the substituent at N(6) were synthesized and evaluated for their cytotoxicity on Huh7, HepG2, FOCUS, Mahlavu liver, MCF7 breast, and HCT116 colon carcinoma cell lines. The purine nucleoside analogues were analyzed initially by an anticancer drug-screening method based on a sulforhodamine B assay. Two nucleoside derivatives with promising cytotoxic activities (11 and 12) were further analyzed on the hepatoma cells. The N(6)-(4-Trifluoromethylphenyl)piperazine analogue 11 displayed the best antitumor activity, with IC(50) values between 5.2 and 9.2 μM. Similar to previously described nucleoside analogues, compound 11 also interferes with cellular ATP reserves, possibly through influencing cellular kinase activities. Furthermore, the novel nucleoside analogue 11 was shown to induce senescence-associated cell death, as demonstrated by the SAβ-gal assay. The senescence-dependent cytotoxic effect of 11 was also confirmed through phosphorylation of the Rb protein by p15(INK4b) overexpression in the presence of this compound.

a b s t r a c tBackground: Hepatocellular carcinoma is the second deadliest cancer with limited treatment options. Loss of PTEN causes the P13K/Akt pathway to be hyperactive which contributes to cell survival and resistance to therapeutics in various cancers, including the liver cancer. Hence molecules targeting this pathway present good therapeutic strategies for liver cancer. Hypothesis: It was previously reported that Cardiac glycosides possessed antitumor activity by inducing apoptosis of multiple cancer cells through oxidative stress. However, whether Cardiac glycoside Lanatoside C can induce oxidative stress in liver cancer cells and induce cell death both in vitro and in vivo remains unknown. Methods: Cell viability was measured by SRB assay. Cell death analysis was investigated by propidium iodide staining with flow cytometry and PARP cleavage. DCFH-DA staining and cytometry were used for intracellular ROS measurement. Protein levels were analyzed by western blot analysis. Antitumor activity was investigated on mice xenografts in vivo. Results: In this study, we found that Cardiac glycosides, particularly Lanatoside C from Digitalis ferruginea could significantly inhibit PTEN protein adequate Huh7 and PTEN deficient Mahlavu human liver cancer cell proliferation by the induction of apoptosis and G2/M arrest in the cells. Lanatoside C was further shown to induce oxidative stress and alter ERK and Akt pathways. Consequently, JNK1 activation resulted in extrinsic apoptotic pathway stimulation in both cells while JNK2 activation involved in the inhibition of cell survival only in PTEN deficient cells. Furthermore, nude mice xenografts followed by MRI showed that Lanatoside C caused a significant decrease in the tumor size. In this study apoptosis induction by Lanatoside C was characterized through ROS altered ERK and Akt pathways in both PTEN adequate epithelial and deficient mesenchymal liver cancer cells. Conclusion:The results indicated that Lanatoside C could be contemplated in liver cancer therapeutics, particularly in PTEN deficient tumors. This is due to Lanatoside C's stress inducing action on ERK and Akt pathways through differential activation of JNK1 and JNK2 by GSK3β.

The development of new biosensor technologies and their active use as wearable devices have offered mobility and flexibility to conventional western medicine and personal fitness tracking. In the development of biosensors, transducers stand out as the main elements converting the signals sourced from a biological event into a detectable output. Combined with the suitable bio-receptors and the miniaturization of readout electronics, the functionality and design of the transducers play a key role in the construction of wearable devices for personal health control. Ever-growing research and industrial interest in new transducer technologies for point-of-care (POC) and wearable bio-detection have gained tremendous acceleration by the pandemic-induced digital health transformation. In this article, we provide a comprehensive review of transducers for biosensors and their wearable applications that empower users for the active tracking of biomarkers and personal health parameters.

Multifunctional nanoparticles based on a green emitting, hydrophobic conjugated polymer, poly[(9,9-bis{propeny}fluorenyl-2,7-diyl)-co-(1,4-benzo-{2, 1,3}-thiodiazole)] (PPFBT), that acts both as a fluorescent reporter and a matrix to accommodate an anti-cancer compound, camptothecin (CPT), were prepared, characterized and their potential as a fluorescent probe for cell imaging and as a drug delivery vehicle were evaluated via in vitro cell assays. The cell viability of human hepatocellular carcinoma cell line (Huh7) was investigated in the absence and presence of CPT with sulforhodamine B (SRB) and real-time cell electronic sensing (RT-CES) cytotoxicity assays. © 2014 The Royal Society of Chemistry

Novel 9-(substituted amino/piperazinoethyl)adenines (4-12), 6-(substituted piperazino/amino)purines (15-27), 9-(p-toluenesulfonyl/cyclopentyl/ethoxycarbonylmethyl)-6-(substituted amino/piperazino)purines (28-34, 36, 37, 38-41) were synthesized and evaluated initially for their cytotoxic activities on liver Huh7, breast T47D and colon HCT116 carcinoma cells. N(6)-(4-Trifluoromethylphenyl)piperazine derivative (17) and its 9-(p-toluene-sulfonyl)/9-cyclopentyl analogues (28, 36) had promising cytotoxic activities. Compounds 17, 28 and 36 were further analysed for their cytotoxicity in a panel of a liver cancer cell lines. The compound 36 had better cytotoxic activities (IC50 ≤ 1 μM) than the nucleobase 5-FU and nucleosides fludarabine, cladribine, and pentostatine on Huh7 cells. Cytotoxicity induced by 36 was later identified as senescence associated cell death by SA-β-Gal assay.