Natural borneol is a novel chemosensitizer that enhances temozolomide-induced anticancer efficiency against human glioma by triggering mitochondrial dysfunction and reactive oxide species-mediated oxidative damage

Abstract

BackgroundTemozolomide (TMZ)-based chemotherapy represents an effective way for treating human glioma. However, its clinical application is limited because of its side effects and resistance to standard chemotherapy. Hence, the search for novel chemosensitizers to augment their anticancer efficiency has attracted much attention. Natural borneol (NB) has been identified as a potential chemosensitizer in treating human cancers. However, the synergistic effect and mechanism of NB and TMZ in human glioma have not been investigated yet.Materials and methodsU251 human glioma cells were cultured, and the cytotoxicity and apoptosis of NB and/or TMZ were examined by MTT assay, flow cytometric analysis and Western blot. Nude mice tumor model was also employed to evaluate the in vivo anticancer effect and mechanism.ResultsThe results showed that the combined treatment of NB and TMZ more effectively inhibited human glioma growth via triggering mitochondria-mediated apoptosis in vitro, accompanied by the caspase activation. Combined treatment of NB and TMZ also caused mitochondrial dysfunction through disturbing Bcl-2 family expression. Further investigation revealed that NB enhanced TMZ-induced DNA damage through inducing reactive oxide species (ROS) overproduction. Moreover, glioma tumor xenograft growth in vivo was more effectively inhibited by the combined treatment with NB and TMZ through triggering apoptosis and anti-angiogenesis.ConclusionTaken together, our findings validated that the strategy of using NB and TMZ could be a highly efficient way to achieve anticancer synergism.

Natural borneol sensitizes human glioma cells to cisplatin-induced apoptosis by triggering ROS-mediated oxidative damage and regulation of MAPKs and PI3K/AKT pathway

“…Cisplatin is one of the most common chemodrugs that can inhibit cancer cell proliferation by inducing caspase-mediated apoptosis (Zhang et al 2014). Previous studies showed the potential of NB in enhancing chemodrug-induced apoptosis Liu et al 2018;Meng et al 2018). Here, we provide convincing evidence that NB potentiated the anticancer efficacy of cisplatin through the induction of caspase-9-mediated cell apoptosis.…”

“…ROS is a critical upstream initiator in cellular signalling cascades, which modulate various cellular events, including cell growth, metastasis, and apoptosis (Apel and Hirt 2004;Pelicano et al 2004). Previous studies have shown that the accumulation of intracellular ROS is closely related to NB-mediated chemo-sensitization (Zhang et al 2014;Liu et al 2018). Herein, our data demonstrated that the combined treatment of cisplatin with NB remarkably increased the intracellular accumulation of ROS in comparison with single treatment.…”

“…NB effectively improves the permeability of drugs by regulating intestinal mucous or blood-brain barrier (Cai et al 2008;Duan et al 2016;Xing et al 2016). NB can also enhance the efficacy of chemo-drugs against various cancer cell lines by increasing the intracellular drug accumulation and modulating ROS-mediated DNA damage with the involvement of MAPKs activation and Akt inactivation Liu et al 2018;Meng et al 2018). The action of NB in chemo-sensitization is constantly being confirmed.…”

Anti-Cancer Potential of Cannabinoids, Terpenes, and Flavonoids Present in Cannabis

“…Acted synergistically with curcumin-based drugs [251,252]. Acted synergistically with temozolomide [253].…”

Borneol promotes apoptosis of human glioma cells by regulating mTORC1 / eIF4E / HIF-1a pathway

“…However, clinically, the desired effect of postoperative radiotherapy or chemotherapy are often difficult to achieve mainly due to the frequent development of tolerance to radiation or chemotherapy in tumor cells.Previous research has shown that borneol can open the blood-brain tumor barrier by regulating the expression of TJPs protein[25]. In addition, studies have revealed the role of borneol as a new type of chemotherapy sensitizer inducing mitochondrial dysfunction and oxidative damage, which promotes the anticancer effect of temozolomide on human glioma cells[26]. However, it is still unclear whether borneol could exert an apoptosis effect on malignant gliomas.…”