GDI2 is a target of paclitaxel that affects tumorigenesis of prostate cancer via the p75NTR signaling pathway.

BACKGROUND: Prostate cancer (PCa) refers to malignant tumors derived from prostate epithelial cells, whose morbidity and mortality rates have been increasing every year. Although new drugs for treating prostate cancer continue to emerge, the unclear mechanism underlying drug targets limits this therapy, thereby constraining identification of effective therapeutic targets. Although GDP dissociation inhibitor 2(GDI2) is highly expressed and closely associated with occurrence and development of many tumors, its role in prostate cancer remains unclear. In this study, we investigated the role of GDI2 and elucidated its underlying mechanism of action in prostate cancer. Moreover, we screened chemotherapeutic drugs that affect GDI2 expression with a view of identifying novel targets for diagnosis and treatment of prostate cancer. METHODS: We performed sequence analyses and functional assays to precisely elucidate the GDI2 role in prostate cancer. Moreover, we induced tumorigenesis in nude mice to verify the role of GDI2 in vivo. Finally, we used the CCK8 assay to ascertain the most suitable IC50 across the three drugs and performed quantitative real time polymerase chain reaction (qRT-PCR) and Western Blot to analyze the effects of drugs on expression of GDI2, p75NTR, and p-NFκB. RESULTS: GDI2 was up-regulated in prostate cancer cells and tissues. Knocking down GDI2 suppressed cell proliferation but promoted cell apoptosis. Interestingly, knocking down GDI2 activated the p75NTR signaling pathway, indicating, for the first time, that p75NTR is negatively correlated with GDI2 expression. CONCLUSION: Taken together, these results indicate that GDI2 is a therapeutic target of paclitaxel. Knocking down of GDI2 inhibits cell proliferation and promotes cell apoptosis via the p75NTR signaling pathway in prostate cancer. Notably, paclitaxel inhibits GDI2 expression, implying that GDI2 may be a promising therapeutic target in prostate cancer.

Synthesis of Zinc oxide nanoparticles from Marsdenia tenacissima inhibits the cell proliferation and induces apoptosis in laryngeal cancer cells (Hep-2).

Biosynthesis of Zinc oxide nanoparticles (ZnONPs) from natural plants stands as a promising nanodrug delivery system in cancer therapeutics. Marsdenia tenacissima (M.t), a Chinese medicinal plant has been extensively used as clinical remedy for treating several types of cancer. In this present study, ZnONPs were synthesized from Marsdenia tenacissima and its anti cancer potency was assessed against in vitro laryngeal cancer cell line Hep-2. The biosynthesized Marsdenia tenacissima Zinc Oxide Nanoparticles [M.t-ZnONPs] was characterized using UV-visible Spec, SEM, TEM and EDAX analysis. The cytotoxic and apoptotic inducing potential of M.t-ZnONPs was assessed by MTT assay and staining such as DCFH-DA, AO/EtBr, Rhodamine 123, DAPI and comet assay. The anticancer potential of M.t-ZnONPs was analysed by Real time PCR analysis of proapoptotic, antiapoptotic and caspases proteins. Our present findings showed characteristic and morphological representation of synthesized M.t-ZnONPs by UV-visible Spec, SEM, TEM and EDAX analysis. M.t-ZnONPs exhibits its cytotoxicity by inhibiting the viability of Hep-2 cells and IC50 value was obtained by MTT assay. The results of apoptotic staining techniques in M.t-ZnONPs treated Hep-2 cells confirm with excess ROS generation, disruption of mitochondrial membrane potential and nuclear damage. The apoptotic inducing potential of M.t-ZnONPs was also evidenced by upregulation of proapoptotic proteins Bax, Caspase 3 & 9 and downregultion of antiapoptotic protein Bcl-2 by RT-PCR analysis. Finally, these results suggested that biosynthesized M.t-ZnONPs is an effective anticancer agent which induces apoptosis in Hep-2 laryngeal cell line and thus conclude that M.t-ZnONPs, a valid anticancer strategy in treating various cancer.

Multifunctional Wearable Device Based on Flexible and Conductive Carbon Sponge/Polydimethylsiloxane Composite.

Wearable devices that can be used to monitor personal health, track human motions, and provide thermotherapy, etc., are highly desired in personalized healthcare. In this work, a multifunctional wearable "wrist band" which works as both heater for thermotherapy and sensor for personal health and motion monitoring is fabricated from a flexible and conductive carbon sponge/polydimethylsiloxane (CS/PDMS) composite. The key functional material of the wrist band, namely, the conductive CS, is synthesized from waste paper by a freeze-drying and high-temperature pyrolysis process. When the wrist band works as a heater under 15 V, a stable temperature difference of 20 °C is achieved between the wrist band and the ambient. When the wrist band serves as a wearable strain sensor, the wrist band exhibits fast and repeatable response and excellent durability within the strain range of 0-20% and the working frequency of 0.01-10 Hz. Finally, the typical applications of the multifunctional wearable wrist band, as a heater for thermotherapy and a sensor for blood pulse, breathe, and walk monitoring, are demonstrated. Due to its low cost, high flexibility, moderate conductivity, and excellent strain sensibility, the as-prepared wearable device based on the CS/PDMS composite is promising to be applied for the provision of personal healthcare.

Pseudolaric acid B induces apoptosis via proteasome-mediated Bcl-2 degradation in hormone-refractory prostate cancer DU145 cells.

Pseudolaric acid B (PAB), a natural diterpene acid present in the traditional Chinese medicinal herb Tu-Jin-Pi, exerted anticancer effects on various cancer cells. However, the effect of PAB on DU145 cells, an in vitro model of hormone-refractory prostate cancer (HRPC), has not been reported previously. In the study, PAB significantly suppressed proliferation of DU145 cells in a dose-dependent manner without obvious cytotoxicity. IC(50) values of 0.89 ± 0.18 and 0.76 ± 0.15 µM at 48h was determined by Cell counting kit (CCK-8) assay and clone formation assay, respectively. PAB also induced DU145 cells apoptosis as confirmed by typical morphological changes and Annexin V-FITC staining. Furthermore, we demonstrated that PAB caused a concentration-dependent elevation of reactive oxygen species (ROS) level in DU145 cells, and N-acetyl-l-cysteine (NAC, a well-known ROS scavenger) could block PAB-induced ROS generation and apoptosis. Western blotting and/or caspase activity data indicated that PAB downregulated anti-apoptotic Bcl-2 protein and activated caspase-9 and caspase-3, which were largely rescued by NAC or MG-132 (proteasome inhibitor). Taken together, these findings provide the first evidence that PAB may inhibit growth of HRPC DU145 cells and induce apoptosis through ROS generation and Bcl-2 degradation via the activation of the ubiquitin-proteasome pathway.