prostate, uterus, and vascular endothelium. Therefore, this receptor is dominant in cognitive function, memory, anxiety, pain, motor regulation, and endocrine regulation (Dhopeshwarkar and Mackie, 2014). Meanwhile, high expression of CNR2 is found in the immune system cells, but it is also functionally expressed in the brain (Feng et al., 2015;Elbaz et al., 2017). The different tissue distributions of CNR1 and CNR2 allow different receptor effects with selective and specific activation pathways. Both types of CNR are highly expressed in various cancer tissues, but CNR2 plays a more critical role in carcinogenesis and

Objective: To determine the effect of rice bran extract (RBE) in combination with doxorubicin on 4T1 triple-negative breast cancer cells and NIH-3T3 cells. Methods: RBE was obtained by maceration with n-hexane. The phytochemical profile of RBE was observed using highperformance liquid chromatography. Cytotoxic effect of RBE was evaluated through MTT assay. In addition, flow cytometry was used for cell cycle and apoptosis analysis. Cellular senescence was observed using SA-β-Gal assay and intracellular reactive oxygen species (ROS) levels were evaluated using DCFDA staining. The pro-oxidant property of RBE was also evaluated through 1-chloro- 2,4-dinitrobenzene spectrophotometry and molecular docking. Results: RBE was obtained with a yield of 18.42% w/w and contained tocotrienols as the major compound. RBE exerted no cytotoxic effect on 4T1 and NIH-3T3 cells. However, RBE in combination with doxorubicin decreased 4T1 cell viability synergistically (combination index<0.9) and induced apoptosis and senescence on 4T1 cells. RBE significantly decreased senescence in doxorubicin-treated NIH-3T3 cells. Additionally, RBE did not increase ROS levels in doxorubicin-treated 4T1 cells. Meanwhile, the combination of RBE and doxorubicin reduced ROS levels in NIH-3T3 cells. RBE significantly reduced glutathione-S-transferase activity and alpha-tocotrienol interacted with glutathione-S- transferase in the glutathione binding site. Conclusions: Rice bran may be used as a co-chemotherapeutic agent to improve the therapeutic effectiveness of doxorubicin while protecting against the cellular senescence effects of doxorubicin on healthy cells.

Background: Lactate dehydrogenase B (LDHB), a typical oxidoreductase for converting lactate to pyruvate in the glycolysis process, takes a complex function in the progression of cancer cells. Even so, the profile of LDHB relevance in colon adenocarcinoma (COAD) remains ambiguous. Hence this study analyzed the expression and co-expression profile of LDHB, and its immune correlation in COAD.Materials and method: The mRNA expression and co-expression of LDHB in COAD were retrieved from UALCAN. The immune infiltration levels of LDHB from B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in COAD were assessed using the TIMER database. For assessing gene ontology and the KEGG pathway, DAVID v6.8 was utilized. The protein-protein interaction of LDHB-correlated genes was analyzed using STRINGDB and Cytoscape.Results: Significantly high expression of LDHB in COAD was spotted in several sample types and associated with a poor overall survival rate. Further, LDHB corresponded to the level of CD4+, macrophages, and myeloid-derived suppressor cell (MDSC) immune infiltrating cells. The co-expression of LDHB was associated with several essential genes for cell cycle progression.Conclusion: The findings of this study indicate an upcoming involvement of LDHB in COAD tumorigenesis and prognosis. Additionally, this study highlights the immune correlation of LDHB in COAD as preliminary data in developing diagnosis and treatment with a novel immune checkpoint in COAD.Keywords: lactate dehydrogenase, colon adenocarcinoma, expression, survival, immune