Context: Cisplatin-based chemotherapy was widely used in treating human malignancies. However, side effects and chemoresistance remains the major obstacle. Objective: To verify whether natural borneol (NB) can enhance cisplatin-induced glioma cell apoptosis and explore the mechanism. Materials and methods: Cytotoxicity of cisplatin and/or NB towards U251 and U87 cells were determined with the MTT assay. Cells were treated with 0.25–80 μg/mL cisplatin and/or 5–80 μM NB for 48 h. The effects of NB and/or cisplatin on apoptosis and cell cycle distribution were quantified by flow cytometric analysis. Protein expression was detected by western blotting. ROS generation was conducted by measuring and visualising an oxidation-sensitive fluorescein DCFH-DA. Results: NB synergistically enhanced the anticancer efficacy of cisplatin in human glioma cells. Co-treatment of 40 μg/mL NB and 40 μg/mL cisplatin significantly inhibited U251 cell viability from 100% to 28.2% and increased the sub-G1 population from 1.4% to 59.3%. Further detection revealed that NB enhanced cisplatin-induced apoptosis by activating caspases and triggering reactive oxygen species (ROS) overproduction as evidenced by the enhancement of green fluorescence intensity from 265% to 645%. ROS-mediated DNA damage was observed as reflected by the activation of ATM/ATR, p53 and histone. Moreover, MAPKs and PI3K/AKT pathways also contributed to co-treatment-induced U251 cell growth inhibition. ROS inhibition by antioxidants effectively improved MAPKs and PI3K/AKT functions and cell viability, indicating that NB enhanced cisplatin-induced cell growth in a ROS-dependent manner. Discussion and conclusions: Natural borneol had the potential to sensitise human glioma cells to cisplatin-induced apoptosis with potential application in the clinic.

Homocysteine (Hcy) as an independent risk factor contributes to the occurrence and development of human cardiovascular diseases (CVD). Induction of oxidative stress and apoptosis was commonly accepted as the major mechanism in Hcy-induced cardiotoxicity. Astaxanthin (ATX) as one of the most powerful antioxidants exhibits novel cardioprotective potential against Hcy-induced endothelial dysfunction. However, the protective effect and mechanism of ATX against Hcy-induced cardiotoxicity in cardiomyocytes have not been elucidated yet. Herein, H9c2 rat cardiomyocytes and Hcy-injured animal model were employed in the present study. The MTT, flow cytometry analysis (FCM), TUNEL-DAPI and western blotting results all demonstrated that ATX significantly alleviated Hcy-induced cytotoxicity in H9c2 cells through inhibition of mitochondria-mediated apoptosis. The JC-1 and Mito-tracker staining both revealed that ATX pre-treatment blocked Hcy-induced mitochondrial dysfunction by regulating Bcl-2 family expression. Moreover, DCFH-DA and Mito-SOX staining showed that ATX effectively attenuated Hcy-induced oxidative damage via scavenging intracellular reactive oxygen species (ROS). Importantly, the ELISA and immunohistochemical results indicated that Hcy-induced cardiotoxicity in vivo was also significantly inhibited by ATX through inhibition of oxidative damage and apoptosis, and improvement of the angiogenesis. Taken together, our results demonstrated that ATX suppressed Hcy-induced cardiotoxicity in vitro and in vivo by inhibiting mitochondrial dysfunction and oxidative damage. Our findings validated the strategy of using ATX may be a highly efficient way to combat Hcy-mediated human CVD.

Doxorubicin (DOX) as a first-line chemotherapeutic drug has been widely used for therapy of human cancers. However, side effects and chemo-resistance severely blocked its clinic application. Herein, natural borneol (NB) as a novel monoterpenoid chemosensitizer was found to have the potential to increase the blood brain barrier (BBB) permeability and intracellular uptake of DOX in vitro, and synergistically enhanced DOX-induced cytotoxicity in human glioma cells. NB treatment significantly potentiated DOX-induced G2/M cell cycle arrest by triggering reactive oxygen species (ROS)-mediated DNA damage. NB also enhanced DOX-induced dysfunction of MAPKs and PI3 K/AKT pathways. Furthermore, U251 human glioma xenograft growth in vivo was also effectively inhibited by combined treatment of DOX with NB through induction of G2/M-phase arrest and antiangiogenesis. Taken together, our finding validated that NB could act as novel chemosensitizer to enhance DOX-induced anticancer efficacy, and strategy of using NB and DOX could be a high efficient way in therapy of human cancers.

Accumulated evidences have verified that cancer chemotherapy may increase the risk of osteoporosis and severely affected the life quality. Osteoclasts hyperactivation was commonly accepted as the major pathogenesis of osteoporosis. However, the role of osteoblasts dysfunction in osteoporosis was little investigated. Our previous study has confirmed that selenium-containing protein from selenium-enriched Spirulina platensis (Se-SP) exhibited enhanced hepatoprotective potential through inhibiting oxidative damage. Herein, the protective effect of Se-SP against cisplatin-induced osteoblasts dysfunction in MC3T3-E1 mouse preosteoblast was investigated, and the underlying mechanism was evaluated. The results indicated that cisplatin dramatically decreased cell viability of preosteoblast by triggering mitochondria-mediated apoptosis pathway. Cisplatin treatment also caused mitochondrial dysfunction and reactive oxide species (ROS)-mediated oxidative damage. However, Se-SP pre-treatment effectively prevented MC3T3-E1 cells from cisplatin-induced mitochondrial dysfunction by balancing Bcl-2 family expression and regulating the opening of mitochondrial permeability transition pore (MPTP), attenuated cisplatin-induced oxidative damage through inhibiting the overproduction of ROS and superoxide anion, and eventually reversed cisplating-induced early and late apoptosis by inhibiting PARP cleavage and caspases activation. Our findings validated that Se-SP as a promising Se species could be a highly effective way in the chemoprevention and chemotherapy of oxidative damage-mediated bone diseases.

Elevated plasma level of homocysteine (Hcy) represents an independent risk for neurological diseases, and induction of oxidative damage is considered as one of the most important pathomechanisms. Astaxanthin (ATX) exhibits strong antioxidant activity in kinds of experimental models. However, the potential of ATX against Hcy-induced neurotoxicity has not been well explored yet. Herein, the neuroprotective effect of ATX against Hcy-induced neurotoxicity in rat hippocampal neurons was examined, and the underlying mechanism was evaluated. The results showed that ATX pre-treatment completely reversed Hcy-induced neurotoxicity through inhibiting cell apoptosis in rat primary hippocampal neurons. The mechanical investigation revealed that ATX effectively blocked Hcy-induced mitochondrial dysfunction by regulating Bcl-2 family and opening of mitochondrial permeability transition pore (MPTP). ATX pre-treatment also attenuated Hcy-induced oxidative damage via inhibiting the release of intracellular reactive oxide species (ROS) and superoxide anion through regulating MPTP opening. Moreover, normalization of MAPKs and PI3K/AKT pathways also contributed to ATX-mediated protective effects. Taken together, these results above suggested that ATX has the potential to reverse Hcy-induced neurotoxicity and apoptosis by inhibiting mitochondrial dysfunction, ROS-mediated oxidative damage and regulation of MAKPs and AKT pathways, which validated the strategy of using ATX could be a highly effective way in combating Hcy-mediated neurological disorders.