Brucea javanica oil emulsion improves the effect of radiotherapy on esophageal cancer cells by inhibiting cyclin D1-CDK4/6 axis

Abstract

BACKGROUND Esophageal cancer is one of the most common cancers around the world, and it has high incidence and mortality rates. The conventional therapy for esophageal cancer is radiotherapy, although its effect is highly limited by the resistance of esophageal cancer cells. Thus, strong radiosensitizers can be very crucial during radiotherapy against esophageal cancer. Brucea javanica oil emulsion (BJOE) is a widely used drug against various cancers, such as liver, colon, and ovarian cancer. However, its anti-cancer effect and mechanism and the use of BJOE as a radiosensitizer have not been explored in esophageal cancer. AIM To evaluate the anti-cancer effect and mechanism of BJOE and explore the potential use of BJOE as a radiosensitizer during radiotherapy. METHODS The inhibitory effect of BJOE and its enhancement function with radiation on cell viability were examined with the calculated half-maximal effective concentration and half-maximal lethal concentration. The influence of BJOE on cell migration and invasion were measured with EC109 and JAR cells by wound-healing and transwell assay. Clonogenesis and apoptotic rate, which was measured by Hoechst staining, were investigated to confirm its enhancement function with radiation. To investigate the molecular pathway underlying the effect of BJOE, the expressions of several apoptosis- and cycle-related proteins was detected by western blotting. RESULTS Our results demonstrated that BJOE inhibited the growth of esophageal cancer cell lines more than normal cell lines, and it markedly reduced migration and invasion in esophageal cancer cells (EC109 and JAR). Moreover, it promoted cell apoptosis and enhanced the effect of radiotherapy against esophageal cancerous cells. In the viability test, the values of half-maximal effective concentration and half-maximal lethal concentration were reduced. Compared to the control, only around 1/5 colonies formed when using BJOE and radiation together in the clonogenic assay. The apoptotic rate in EC109 was obviously promoted when BJOE was added during radiotherapy. Our study suggests that the expression of the apoptosis-proteins Bax and p21 were increased, while the expression of Bcl-2 was stable. Further detection of downstream proteins revealed that the expression of cyclin D1 and cyclin-dependent kinase 4/6 were significantly decreased. CONCLUSION BJOE has a strong anti-cancer effect on esophageal cancer and can be used as a radiosensitizer to promote apoptosis in cancerous esophageal cells via the cyclin D1-cyclin-dependent kinase 4/6 axis.

[Retracted] The Promotional Effect of Hollow MnO2 with Brucea Javanica Oil Emulsion (BJOE) on Endometrial Cancer Apoptosis

“…As uncovered in the previous study, BJOE could regulate the relative tumor genes to kill cancer cells directly [ 22 – 25 ]. Besides, it had also been verified to repress the resistance reaction of tumor cells to chemotherapy and significantly improve body immunity [ 26 ]. To further understand the function of BJOE on endometrial cancer cells, the cellular activity of RL95-2 was observed for 48 h after the single BJOE (50 μ g/mL), the single H-MnO 2 -PEG, or the combination of H-MnO 2 -PEG/BJOE by CCK-8 assay and DAPI assay.…”

miR-29a overexpresion induces apoptosis through targeting VEGF in hepatocellular carcinoma

“…Cyclin D1 regulates the activity of Cyclin-dependent kinase (CDKs) [20,21]. Cyclin D1 is the functional subunit of CDK4 and regulates the G1/S transition of cells [22]. CDK4 belongs to the Ser/Thr protein kinase family.…”

Brusatol‐Enriched Brucea javanica Oil Ameliorated Dextran Sulfate Sodium‐Induced Colitis in Mice: Involvement of NF‐κB and RhoA/ROCK Signaling Pathways

“…Brucea javanica (L.) Merr. (Ya-dan-zi in Chinese, Simaroubaceae) is a crucial Chinese folk medicine widely used for the treatment of dysentery, which was also known as inflammatory bowel disease (IBD) [ 8 , 9 ]. Brucea javanica oil (BJO), an extract of the desiccative ripe fruit of the Brucea javanica (L.) Merr., exhibits various bioactivities, including anti-inflammatory, antimalarial, and antitumor activities [ 10 ].…”