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Targeting melanoma stem cells with the Vitamin E derivative ?-tocotrienol.

ABSTRACT: The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We also showed that a subpopulation of autofluorescent cells expressing the ABCG2 stem cell marker is present in the A375 spheroid culture. Based on these data, we investigated whether ?-TT might target melanoma CSCs. We demonstrated that melanoma cells escaping the antitumor activity of ?-TT are completely devoid of the ability to form melanospheres. In contrast, cells that escaped vemurafenib treatment show a higher ability to form melanospheres than control cells. ?-TT also induced disaggregation of A375 melanospheres and reduced the spheroidogenic ability of sphere-derived cells, reducing the expression of the ABCG2 marker. These data demonstrate that ?-TT exerts its antitumor activity by targeting the CSC subpopulation of A375 melanoma cells and might represent a novel chemopreventive/therapeutic strategy against melanoma.

SUBMITTER: Marzagalli M

PROVIDER: S-EPMC5766483 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol.

Marzagalli Monica M Moretti Roberta Manuela RM Messi Elio E Marelli Marina Montagnani MM Fontana Fabrizio F Anastasia Alessia A Bani Maria Rosa MR Beretta Giangiacomo G Limonta Patrizia P

Scientific reports 20180112 1

The prognosis of metastatic melanoma is very poor, due to the development of drug resistance. Cancer stem cells (CSCs) may play a crucial role in this mechanism, contributing to disease relapse. We first characterized CSCs in melanoma cell lines. We observed that A375 (but not BLM) cells are able to form melanospheres and show CSCs traits: expression of the pluripotency markers SOX2 and KLF4, higher invasiveness and tumor formation capability in vivo with respect to parental adherent cells. We a ...[more]

PMID: 29330434

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Project description:PurposeChronic hemodialysis patients experience accelerated atherosclerosis contributed to by dyslipidemia, inflammation, and an impaired antioxidant system. Vitamin E tocotrienols possess anti-inflammatory and antioxidant properties. However, the impact of dietary intervention with Vitamin E tocotrienols is unknown in this population.Patients and methodsA randomized, double-blind, placebo-controlled, parallel trial was conducted in 81 patients undergoing chronic hemodialysis. Subjects were provided daily with capsules containing either vitamin E tocotrienol-rich fraction (TRF) (180 mg tocotrienols, 40 mg tocopherols) or placebo (0.48 mg tocotrienols, 0.88 mg tocopherols). Endpoints included measurements of inflammatory markers (C-reactive protein and interleukin 6), oxidative status (total antioxidant power and malondialdehyde), lipid profiles (plasma total cholesterol, triacylglycerols, and high-density lipoprotein cholesterol), as well as cholesteryl-ester transfer protein activity and apolipoprotein A1.ResultsTRF supplementation did not impact any nutritional, inflammatory, or oxidative status biomarkers over time when compared with the baseline within the group (one-way repeated measures analysis of variance) or when compared with the placebo group at a particular time point (independent t-test). However, the TRF supplemented group showed improvement in lipid profiles after 12 and 16 weeks of intervention when compared with placebo at the respective time points. Normalized plasma triacylglycerols (cf baseline) in the TRF group were reduced by 33 mg/dL (P=0.032) and 36 mg/dL (P=0.072) after 12 and 16 weeks of intervention but no significant improvement was seen in the placebo group. Similarly, normalized plasma high-density lipoprotein cholesterol was higher (P<0.05) in the TRF group as compared with placebo at both week 12 and week 16. The changes in the TRF group at week 12 and week 16 were associated with higher plasma apolipoprotein A1 concentration (P<0.02) and lower cholesteryl-ester transfer protein activity (P<0.001).ConclusionTRF supplementation improved lipid profiles in this study of maintenance hemodialysis patients. A multi-centered trial is warranted to confirm these observations.

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Targeting melanoma stem cells with the Vitamin E derivative ?-tocotrienol.

Publications

Targeting melanoma stem cells with the Vitamin E derivative δ-tocotrienol.

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