7‐Epitaxol induces apoptosis in cisplatin‐resistant head and neck squamous cell carcinoma via suppression of AKT and MAPK signalling

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Although cisplatin-based chemotherapy is commonly used in HNSCC, frequent development of cisplatin resistance is a potential cause of poor HNSCC prognosis. In the present study, we investigated the anticancer efficacy of a major paclitaxel metabolite namely 7-Epitaxol in cisplatin-resistant HNSCC. The findings revealed that 7-Epitaxol exerts cytotoxic effects in cisplatin-resistant HNSCC cell lines by inducing cell cycle arrest and intrinsic and extrinsic apoptotic pathways. Specifically, 7-Epitaxol increased Fas, TNF-R1, DR5, DcR3 and DcR2 expressions, reduced Bcl-2 and Bcl-XL (anti-apoptotic proteins) expressions, and increased Bid and Bim L/S (pre-apoptotic proteins) expressions, leading to activation of caspase-mediated cancer cell apoptosis.At the upstream cell signalling level, 7-Epitaxol reduced the phosphorylation of AKT, ERK1/2 and p38 to trigger apoptosis. In vivo results showed that animals treated with 7-Epitaxol show antitumor growth compared to control animals. Taken together, the study demonstrates the potential anticancer efficacy of 7-Epitaxol in inducing apoptosis of cisplatin-resistant HNSCC cells through the suppression of AKT and MAPK signalling pathways.

ITGB3 promotes cisplatin resistance in osteosarcoma tumors

“…It is interesting to note that KEGG pathway enrichment was observed only in the downregulated group (Figure 5F ; Table S3 ). Among these enrichments, some signaling pathways were commonly related to cisplatin resistance in osteosarcomas, such as the mitogen‐activated protein kinase (MAPK) pathway 20 , 21 , 22 , 23 , 24 and vascular endothelial growth factor (VEGF). 25 , 26 , 27 Additionally, 10 hub genes were identified, and their associated signaling pathways were demonstrated (Figure 5G ).…”

Semilicoisoflavone B induces oral cancer cell apoptosis by targeting claspin and ATR‐Chk1 signaling pathways

“…MTT (5 mg/mL) assay was performed as described previously 18 to assess in vitro cytotoxicity of SFB in 5FU‐SAS and 5FU‐SCC9 cell lines. The cells were cultured in 96‐well plates at 1 × 10 4 cells/well concentration overnight, followed by treatment with different concentrations of SFB (0, 25, 50, or 100 μM) of 24, 48, and 72 h. The treated cells were incubated with MTT solution at 37°C for 4 h, and the resulted blue formazan crystals were dissolved in DMSO.…”

Limocitrin increases cytotoxicity of KHYG‐1 cells against K562 cells by modulating MAPK pathway

“…An earlier description of the Annexin V/PI double stain for apoptosis detection was given 21 . The upper wells of a Transwell insert (Greiner Bio‐One, Monroe, NC) were loaded with KHYG‐1 cells after limocitrin treatment at the recommended concentrations.…”

“…An earlier description of the Annexin V/PI double stain for apoptosis detection was given. 21 The upper wells of a Transwell insert (Greiner Bio-One, Monroe, NC) were loaded with KHYG-1 cells after limocitrin treatment at the recommended concentrations. The lower wells of the same insert were supplemented with K562 cells (in RPMI 1640 medium) and incubated using the previously discussed coculture techniques.…”