astaxanthine and Carcinoma--Squamous-Cell

Aberrant activation of the PI3K/Akt signalling pathway, a major driving force of diverse cellular processes has been implicated in tumour development and progression. Here, we report that astaxanthin (AXT), a potent antioxidant ketocarotenoid prevents cancer hallmarks by inhibiting PI3K/Akt and the associated downstream NF-κB and STAT-3 signalling pathways in SCC131 and SCC4 oral cancer cells as well as in the hamster buccal pouch carcinogenesis model. Using small molecule inhibitors of NF-κB, STAT-3 and PI3K and by overexpression of PI3K, we provide evidence to show that AXT inhibits NF-κB and STAT-3 signalling and cancer hallmarks by restraining the kinase activity of PI3K/Akt. Additionally, AXT downregulated the noncoding RNAs (ncRNAs), miR-21 and HOTAIR that influence PI3K/Akt signalling emphasising its modulatory effects on epigenetic regulation. Ethyl cellulose-based AXT nanoparticles showed greater chemotherapeutic efficacy in the hamster oral carcinogenesis model compared to native AXT. We suggest that AXT prevents cell proliferation, apoptosis evasion, invasion and angiogenesis by intercepting the crosstalk between the PI3K/Akt, NF-κB and STAT-3 signalling circuits both in vitro and in vivo. Astaxanthin that abrogates the PI3K/Akt signalling axis, a central hub that orchestrates acquisition of cancer hallmarks is a promising candidate for anticancer drug development.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Mouth Neoplasms; Neovascularization, Pathologic; NF-kappa B; Phosphatidylinositol 3-Kinases; Phosphorylation; Signal Transduction; STAT3 Transcription Factor; Transcription Factor RelA; Xanthophylls

The photothermal effect of a marine-oriented xanthophyll carotenoid, astaxanthin (AXT), was characterized based on its potential absorption of visible laser light and conversion of optical light energy into heat for thermal treatment. As an antioxidant and anticancer agent, AXT extracted from marine material can be utilized for photothermal therapy due to its strong light absorption. The current study investigated the feasibility of the marine-based material AXT to increase the therapeutic efficacy of chemo-photothermal therapy (PTT) by assessing photothermal sessions in both cells and tumor tissues. A quasi-cw Q-switched 80 W 532 nm laser system was utilized to induce thermal necrosis in in vitro and in vivo models. An in vitro cytotoxicity study of AXT was implemented using squamous cell carcinoma (VX2) and macrophage (246.7) cell lines. In vivo PTT experiments were performed on 17 rabbits bearing VX2 tumors on their eyes that were treated with or without intratumoral injection of AXT at a dose of 100 μl (300 μg/ml) followed by laser irradiation at a low irradiance of 0.11 W/cm2. Fluorescence microscopy images revealed cellular death via apoptosis and necrosis owing to the dual chemo-photothermal effects induced by AXT. In vivo experimental results demonstrated that the AXT-assisted irradiation entailed a temperature increase by 30.4°C after tumor treatment for 4 min. The relative variations in tumor volume confirmed that the tumors treated with both AXT and laser irradiation completely disappeared 14 days after treatment, but the tumors treated under other conditions gradually grew. Due to selective light absorption, AXT-assisted laser treatment could be an effective thermal therapy for various drug-resistant cancers.

Topics: Animals; Antineoplastic Agents; Antioxidants; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Survival; Eye Neoplasms; Humans; Laser Therapy; Mice; Photochemotherapy; Rabbits; Xanthophylls

Nowadays esophageal squamous cell carcinoma (ESCC) is primarily treated by a comprehensive approach combining surgical resection and neoadjuvant chemo- or radiotherapy. However, ESCC is resistant to radiation therapy, resulting in its invasion, infiltration, and metastasis. It usually has rapidly progressed and has a poor outcome clinically. The purpose of this study is to determine the potential radiosensitizing effect of astaxanthin (ATX) and explore the underlying mechanisms in ESCC cells in vitro. ESCC cell lines were exposure to irradiation, in the presence or absence of ATX treatment. Cell viability and radiosensitization were tested by CCK8 assay and clonogenic survival assay, respectively. Cell apoptosis and the changes of cell cycle distribution were observed by flow cytometry. The protein expression of Bcl2, Bax, CyclinB1, and Cdc2 was examined by western blot analysis. It was shown that ATX improved radiosensitivity of ESCC cells and induced apoptosis and G2/M arrest via inhibiting Bcl2, CyclinB1, Cdc2, and promoting Bax expression. In conclusion, ATX might function as a promising radiosensitizer in ESCC cells by leading to apoptosis and G2/M arrest.

Topics: Apoptosis; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Cell Survival; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Radiation Tolerance; Radiation-Sensitizing Agents; Xanthophylls