Vitamin E reverses multidrug resistance in vitro and in vivo

Tang, Jingling; Fu, Qiang; Wang, Yongjun; Racette, Kelly; Wang, Dun; Liu, Feng

doi:10.1016/j.canlet.2013.04.020

Cited by 63 publications

(48 citation statements)

References 47 publications

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“…In addition to its anticancer activity, described above, the synthetic form of α-tocopherol, TS, may also act as an MDR inhibitor. Treatment of two human MDR cell lines (H460/taxR and KB-8-5) with TS exhibited a significant reversal of the MDR effect compared with paclitaxel alone; however, the inhibition effect was less than that observed with TGPS (59). In agreement with the in vitro findings, the in vivo studies using MDR cell xenograft model showed the ability of TS to overcome MDR when simultaneously administered with paclitaxel (59).…”

Section: Vitamin E As a Chemosensitizer In Cancer Therapysupporting

confidence: 76%

“…Treatment of two human MDR cell lines (H460/taxR and KB-8-5) with TS exhibited a significant reversal of the MDR effect compared with paclitaxel alone; however, the inhibition effect was less than that observed with TGPS (59). In agreement with the in vitro findings, the in vivo studies using MDR cell xenograft model showed the ability of TS to overcome MDR when simultaneously administered with paclitaxel (59). The mechanism by which TS enhanced paclitaxel efficacy was explained by its inhibitory effect on the ATPase activity resulting in increased intracellular accumulation of paclitaxel, without altering the levels of P-gp expression (59).…”

Section: Vitamin E As a Chemosensitizer In Cancer Therapymentioning

confidence: 81%

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Vitamin E Transporters in Cancer Therapy

Alqahtani

Kaddoumi

2014

AAPS J

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Abstract. Besides their potent antioxidant activity, vitamin E isoforms demonstrated multiple therapeutic activities among which is their activity against different cancer types, including breast, prostate, and colon cancers. However, the activity of vitamin E isoforms is limited by their low bioavailability following oral administration. In addition to the low solubility, vitamin E isoforms have been established as substrates for several intestinal and hepatic transport proteins. In this review, we present reported anticancer activity of vitamin E family members and the possible utilization of vitamin E and derivatives as chemosensitizers to reverse multidrug resistance when given as part of a delivery system and/or in combination with anticancer therapeutic drugs. Then, the review discusses disposition of vitamin E members and transport proteins that play a role in determining their systemic bioavailability followed by recent advances in vitamin E formulations and delivery strategies.

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Section: Vitamin E As a Chemosensitizer In Cancer Therapysupporting

confidence: 76%

Section: Vitamin E As a Chemosensitizer In Cancer Therapymentioning

confidence: 81%

Vitamin E Transporters in Cancer Therapy

Alqahtani

Kaddoumi

2014

AAPS J

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“…The increased accumulation of Rh 123 within A2780/Taxol cells may be a result of decreased expression of P-gp or inhibited function of P-gp. In our previous studies (31,32), western blot analyses were performed to assess the effect of Brij 78 and TPGS on the protein expression levels of P-gp. Upon pretreatment with Brij 78 or TPGS, the expression level of P-gp protein was not significantly altered compared with that in control H460/TaxR cells.…”

Section: Ee Of (Cur+pip)-slnsmentioning

confidence: 99%

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro

Tang

Ren

et al. 2016

Oncology Letters

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Abstract. Multidrug resistance (MDR) is a main clinical hurdle for chemotherapy of cancer, and overexpression of P-glycoprotein (P-gp) is a key factor. In the present study, a new co-delivery system for reversing MDR was designed and developed. The system was composed of curcumin (Cur) and piperine (Pip) encapsulated in solid lipid nanoparticles (SLNs) with tocopheryl polyethylene glycol succinate (TPGS) and Brij 78 [(Cur+Pip)-SLNs]. TPGS and Brij 78 could sensitize MDR tumors by inhibiting the P-gp drug efflux system. The combination of Cur and Pip, when administered in SLNs formulations, resulted in a significant enhancement in cytotoxicity and allowed efficient intracellular delivery of the drugs in drug-resistant A2780/Taxol cells. This dual inhibitory strategy may have significant potential in the clinical management of MDR in cancer.

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“…The significant in vivo efficacy might be explained by two occurrences: one is the enhanced accumulation of molecularmatched NEs at the tumor site due to long circulation ( Figure 6), and second that VE and TPGS could induce a significant reversal of MDR. In fact, we found that VE is the key structure of TPGS, responsible for inhibiting P-gp [19]. As for tolerability, no weight loss occurred in the mice treated with the VE-PTX NEs ( Figure 5B).…”

Section: Manipulate the Pk Of Nes With Molecularmatched And Molecular-mmentioning

confidence: 77%

Molecular-Matched Materials for Anticancer Drug Delivery And Imaging

Wang

Tang

et al. 2015

Nanomedicine (Lond.)

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Aim:In this study, we aim to construct nanoformulation with high-cargo loading and controlled serum kinetics. Materials & methods: Molecular-matched materials (MMMs) are established through the conjugation of the functional moiety to a molecule representative of the nanoparticle's core. Molecular-matched nanoemulsions and liposomes were prepared using MMMs. Results: This technique based on MMMs even allows us to efficiently load either hydrophobic or hydrophilic moieties into a hydrophobic core of the nanoparticles. MMMs-based nanoparticles showed marked improvement in serum pharmacokinetics and anticancer effect. Conclusion: The desired performance can be achieved when the hydrophobic anchor of the PEG derivatives and the moiety conjugated to the therapeutic (or imaging) agents are molecularly identical to the core. Keywords: imaging • long circulation • molecular-matched nanoparticles • paclitaxel • PEGylationNanocarriers designed with hydrophobic cores are often useful for delivering hydrophobic drugs but are highly incompatible with hydrophilic imaging probes. Additionally, highly crystalline hydrophobic drugs, such as paclitaxel (PTX), may also be incompatible with these particles. This leads to issues with cargo selectivity and loading efficiency. Other common issues with nanocarriers are uncontrolled cargo release or rapid pharmacokinetic (PK) clearance. Great efforts have been made to remedy these problems; however, no carrier has effectively managed all these issues [1][2][3][4][5]. While many different formulations have been applied to PTX, there has been very little success thus earning it the description 'brickdust' [6]. As to PTX formulation, only Taxol and Abraxane were approved by the US FDA for cancer therapy, but both have some limitations. Taxol requires the use of Cremophor-EL at a ratio of PTX to surfactant of 1/90 (w/w); this dose of Cremophor-EL is well documented to cause serious side effects, including hypersensitivity reactions, nephrotoxicity, cardiotoxicity and neurotoxicity [7,8]. Although Abraxane has several practical advantages over Taxol, such as the significant reduction of toxicity and the increase in the efficiency of PTX loading, Abraxane did not improve the PK of PTX [9,10]. Additionally, there is no evidence that either Abraxane or Taxol can overcome multiple drug resistance (MDR) in cancer. Many efforts have been made to improve the PK of PTX; for example, Sonus Pharmaceuticals developed an injectable, PEGylated PTX nanoemulsion (NE) with vitamin E (VE) as the oil-core. However, this NE failed in a pivotal phase III study conducted in breast cancer patients [11]. Letchford K and Burt HM designed copolymers composed of higher molecular weight hydrophobic blocks that form nanoparticles (NPs). These so-called 'frozen core' particles were expected to better retain PTX, thus leading to prolonged circulation of the drugs. Unfortunately, their results indicated PTX was still eliminated from the blood rapidly due to instability of the carrier upon injection [12]. Therefore, the rat...

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Vitamin E reverses multidrug resistance in vitro and in vivo

Cited by 63 publications

References 47 publications

Vitamin E Transporters in Cancer Therapy

Vitamin E Transporters in Cancer Therapy

Solid lipid nanoparticles with TPGS and Brij 78: A co-delivery vehicle of curcumin and piperine for reversing P-glycoprotein-mediated multidrug resistance in vitro

Molecular-Matched Materials for Anticancer Drug Delivery And Imaging

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