Anticancer Effect by Combined Treatment of Artemisia annua L. Polyphenols and Docetaxel in DU145 Prostate Cancer Cells and HCT116 Colorectal Cancer Cells.

Docetaxel (DTX), a semi-synthetic analogue of paclitaxel (taxol), is known to exert potent anticancer activity in various cancer cells by suppressing normal microtubule dynamics. In this study, we examined how the anticancer effect of DTX is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in DU145 prostate cancer cells (mutant p53) and HCT116 colorectal cancer cells (wild-type p53). Here, we show that the anticancer effect of DTX was enhanced more significantly by pKAL in HCT116 cells than in DU145 cells via phase-contrast microscopy, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/propidium iodide-stained cells. Notably, mutant p53 was slightly downregulated by single treatment of pKAL or DTX in DU145 cells, whereas wild-type p53 was significantly upregulated by pKAL or DTX in HCT116 cells. Moreover, the enhanced anticancer effect of DTX by pKAL in HCT116 cells was significantly associated with the suppression of DTX-induced p53 upregulation, increase of DTX-induced phospho-p38, and decrease of DTX-regulated cyclin A, cyclin B1, AKT, caspase-8, PARP1, GM130, NF-κB p65, and LDHA, leading to the increased apoptotic cell death and plasma membrane permeability. Our results suggest that pKAL could effectively improve the anticancer effect of DTX-containing chemotherapy used to treat various cancers expressing wild-type p53.

Comparison of corticocancellous bone graft from the anterolateral metaphysis of the distal radius versus iliac crest for the treatment of unstable scaphoid nonunion with humpback deformity.

BACKGROUND: Corticocancellous bone grafting from the iliac crest is acceptable treatment for unstable scaphoid nonunion with a viable proximal pole. However, harvesting graft from the iliac crest is associated with donor site morbidity and the requirement of general anesthesia. Thus, bone grafting from the anterolateral metaphysis of the distal radius (DR) can be a treatment option. However, no study has compared the clinical effect between the two grafting techniques. METHODS: From 2014 to 2019, patients with unstable scaphoid nonunion with humpback deformity underwent corticocancellous bone grafting from the anterolateral metaphysis of the DR (group DR) or iliac crest (group IC). Humpback deformity was determined by evaluating the scapholunate angle (SLA) ≥ 60°, intrascaphoid angle (ISA) ≥ 45°, and radiolunate angle (RLA) ≥ 15° from preoperative radiographs and computed tomography scans. The SLA, ISA, and RLA served to gauge carpal alignment. The operative time, grip strength, active range of motion (ROM), the Modified Mayo Wrist score (MMWS), and Disabilities of Arm, Shoulder, and Hand (DASH) score were assessed postoperatively. RESULTS: Thirty-eight patients qualified for the study (group DR, 15; group IC, 23). Union rates did not differ by patient subset (group DR, 100%; group IC, 95.7%; P = .827), and grip strength, ROM, MWS, and DASH score were similar between groups at the last follow-up. The operative time (minutes) was significantly shorter in group DR (median, 98; quartiles, 80, 114) than in group IC (median, 125; quartiles, 105, 150, P < .001). The ISA, RLA, and SLA improved postoperatively in both groups (P < 0.001). The degree of restoring carpal alignment, as evaluated by SLA, showed superior correction capability in group DR (median, 25.3% quartiles, 21.1, 35.3, P < 0.05). Donor site complications were not significantly different between the groups. CONCLUSIONS: Corticocancellous bone graft from the anterolateral metaphysis of the DR for unstable scaphoid nonunion is associated with a shorter operation time and comparable results with that from the iliac crest in regard to union, restoration of carpal alignment, and wrist function. LEVEL OF EVIDENCE: Level III.

Artemisia annua L. Polyphenols Enhance the Anticancer Effect of ß-Lapachone in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells.

Recent studies suggest that the anticancer activity of ß-lapachone (ß-Lap) could be improved by different types of bioactive phytochemicals. The aim of this study was to elucidate how the anticancer effect of ß-Lap is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in parental HCT116 and oxaliplatin-resistant (OxPt-R) HCT116 colorectal cancer cells. Here, we show that the anticancer effect of ß-Lap is more enhanced by pKAL in HCT116-OxPt-R cells than in HCT116 cells via a CCK-8 assay, Western blot, and phase-contrast microscopy analysis of hematoxylin-stained cells. This phenomenon was associated with the suppression of OxPt-R-related upregulated proteins including p53 and ß-catenin, the downregulation of cell survival proteins including TERT, CD44, and EGFR, and the upregulation of cleaved HSP90, γ-H2AX, and LC3B-I/II. A bioinformatics analysis of 21 proteins regulated by combined treatment of pKAL and ß-Lap in HCT116-OxPt-R cells showed that the enhanced anticancer effect of ß-Lap by pKAL was related to the inhibition of negative regulation of apoptotic process and the induction of DNA damage through TERT, CD44, and EGFR-mediated multiple signaling networks. Our results suggest that the combination of pKAL and ß-Lap could be used as a new therapy with low toxicity to overcome the OxPt-R that occurred in various OxPt-containing cancer treatments.