The Role of Alpha Tocopheryl Succinate (α-TOS) as a Potential Anticancer Agent

Angulo‐Molina, Aracely; Reyes‐Leyva, Julio; López‐Malo, Aurelio; Hernández, Jesús

doi:10.1080/01635581.2014.863367

Cited by 47 publications

(21 citation statements)

References 67 publications

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“…LMWH inhibits the adhesion between platelets and tumor cells by hindering P‐selectin on activated platelets, thus inhibiting the final stage of the metastatic cascade. Moreover, d ‐α‐tocopheryl succinate (TOS), the most effective form of vitamin E analogues, can inhibit the drug resistance of tumors and increase the apoptosis of various types of cancer cells, including B16F10 melanoma cells . In this study, α‐TOS was confirmed to inhibit the expression of matrix metalloproteinase‐9 (MMP‐9) in B16F10 cells significantly.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

Long

Mei

et al. 2018

Advanced Science

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Metastasis remains the main driver of mortality in patients suffering from cancer because of the refractoriness resulting from the multi‐phase metastatic cascade. Herein, a multifunctional self‐delivering PBA‐LMWH‐TOS nanoparticle (PLT NP) is established that acts as both nanocarrier and anti‐metastatic agent with effects on most hematogenous metastases of cancers. The hydrophilic segment (low molecular weight heparin, LMWH) inhibits the interactions between tumor cells and platelets. The hydrophobic segment (d‐α‐tocopheryl succinate, TOS) could inhibit the expression of matrix metalloproteinase‐9 (MMP‐9) in B16F10 cells which is first reported in this article. Surprisingly, even the blank NPs showed excellent anti‐metastatic capacity in three mouse models by acting on different phases of the metastatic cascade. Moreover, the overexpression of sialic acid (SA) residues on tumor cells is implicated in the malignant and metastatic phenotypes of cancers. Thus, these 3‐aminophenylboronic acid (PBA)‐modified doxorubicin (DOX)‐loaded NPs offer an efficient approach for the treatment of both solid melanomas and metastases. Furthermore, a simple pH‐sensitive “Fructose (Fru)‐blocking” coping strategy is established to reduce the NP distribution in normal tissues and distinctly increases the accumulation in melanoma tumors. These micellar NPs consisting of biocompatible materials offer a promising approach for the clinical therapy of highly invasive solid tumors and metastases.

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Section: Introductionmentioning

confidence: 99%

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

Long

Mei

et al. 2018

Advanced Science

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“…αTS was shown to inhibit cancer cell proliferation while inducing apoptosis in cancer cells via mitochondrial destabilization, without affecting the proliferation of normal cells (Prasad et al., 2003 ). Moreover, it can also enhance the inhibition of tumor growth as in case of ionizing radiation and hyperthermia therapy (Prasad et al., 2003 ; Angulo-Molina et al., 2014 ). Because of the anticancer activities of αTS and its derivatives, they have been used as a component of nanoparticles for cancer therapy (Zeng et al., 2013 ; Tao et al., 2015 ; Zeng et al., 2015 ; Mallick et al., 2016 ; Muddineti et al., 2017 ; Palao-Suay et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

An α-tocopheryl succinate enzyme-based nanoassembly for cancer imaging and therapy

Lee

Cho

2018

Drug Delivery

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Nanoassembly (NA) based on a D-α-tocopherol succinate (αTS) conjugated lysozyme (Lys) (Lys-αTS) was fabricated for tumor-selective delivery of curcumin (CUR) for breast cancer therapy. Lys and αTS were used as a biocompatible enzyme and a hydrophobic residue, respectively, for the preparation of nanocarriers in this study. Compared with CUR-loaded cross-linked Lys (c-Lys/CUR) NA, Lys-αTS/CUR NA exhibited a smaller hydrodynamic size (213 nm mean diameter), a narrower size distribution, and a more spherical shape. Sustained drug release was observed from the Lys-αTS/CUR NA for five days at a normal physiological pH (pH 7.4). The developed Lys-αTS/CUR NA showed enhanced cellular accumulation, antiproliferative effects, and apoptotic efficacies in MDA-MB-231 human breast adenocarcinoma cells. According to the results of optical imaging test in the MDA-MB-231 tumor-bearing mouse models, the Lys-αTS/CUR NA-injected group exhibited a more tumor-selective accumulation pattern, rather than being distributed in the normal tissues and organs. The observed tumor targetability of Lys-αTS/CUR was further studied, which revealed improved in vivo anticancer activities (better inhibition of tumor growth and induction of apoptosis in the tumor tissue) after an intravenous administration in the MDA-MB-231 tumor-bearing mouse models. All these results indicate that the newly developed enzyme-based nanocarrier, the Lys-αTS NA, can be a promising candidate for the therapy of breast cancers.

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“…Pro-apoptotic effect of α-TS is well studied in cancer cell cultures mainly due to the works of J. Neuzil et al [23] that found the basis for the use of this compound as an antitumor agent. There are numerous and varied assumed mechanisms of α-TS action [24,25].…”

Section: Resultsmentioning

confidence: 99%

The sensitivity of cells with the various level of NAD(P)H:quinone oxidoreductase 1

Parshykov¹

2015

Ukr.Biochem.J.

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The effects of α-tocopherol with shortened to 6 carbon atoms side chain ), α-tocopherol succinate (α-Ts) and quinonimine 2,6-dichlorophenolindophenol (DCPIP) on DT-diaphorase activity and viability of rat thymocytes, splenocytes and hepatocytes were investigated. It was shown that the lowest basal activity of the enzyme is inherent in splenocytes. In comparison to splenocytes, DT-diaphorase activity was 1.4 and 5 times higher in thymocytes and hepatocytes, respectively. It was found that the sensitivity of cells to the cytotoxic effect of DCPIP was inversely proportional to the basal level of DT-diaphorase activity and accompanied by its activation with subsequent inhibition at non-toxic and toxic concentrations, respectively. hepatocytes were least sensitive to the cytotoxic effect of α-Toc-C 6 . In thymocytes and splenocytes α-Toc-C 6 exerts inhibitory effects on DT-diaphorase, whereas in hepatocytes an increased activity of the enzyme was observed, which probably caused their high survival rate. simultaneous induction of cytochrome P450 enzyme expression by α-Toc-C 6 in hepatocytes is also possible. Cytotoxic effect of α-Ts does not depend on the basal level of DT-diaphorase activity in cells, is not accompanied by its induction and it is most likely determined by the non-specific esterase activity. k e y w o r d s: α-tocopherol with shortened to 6 carbon atoms side chain (α-Toc-C 6 ), α-tocopherol succinate (α-Ts), quinonimines, thymocytes, splenocytes, hepatocytes, DT-diaphorase.

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The Role of Alpha Tocopheryl Succinate (α-TOS) as a Potential Anticancer Agent

Cited by 47 publications

References 67 publications

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

Enhanced Melanoma‐Targeted Therapy by “Fru‐Blocked” Phenyboronic Acid‐Modified Multiphase Antimetastatic Micellar Nanoparticles

An α-tocopheryl succinate enzyme-based nanoassembly for cancer imaging and therapy

The sensitivity of cells with the various level of NAD(P)H:quinone oxidoreductase 1

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