Enhancement of doxorubicin concentration in the M5076 ovarian sarcoma cells by cucurbitacin E co-treatment

Sadzuka, Yasuyuki; Hatakeyama, Haruna; Sonobe, Takashi

doi:10.1016/j.ijpharm.2009.08.040

Cited by 23 publications

(15 citation statements)

References 30 publications

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“…These findings suggest that STAT3 pathway may be involved in the molecular signaling of EMT and distant metastasis in head and neck cancer in vivo. Moreover, some reports have shown the synergistic effect of cucurbitacins with known chemotherapeutic agents, such as doxorubicin (35). Although the molecular mechanism of HNSCC-CSC or CD44 + ALDH1 + is still unclear, there is a need to further investigate targeting IL-6/JAK/STAT3 signaling as well as other paracrine or autocrine factors and radiochemoattractants involved in the tumor microenvironment that biologically impact HNSCC progression.…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Chen

Huang

et al. 2010

Molecular Cancer Therapeutics

123

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Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer worldwide. Signal transducers and activators of transcription 3 (STAT3) signaling is reported to promote tumor malignancy and recurrence in HNSCC. Cucurbitacins, triterpenoid derivatives, are strong STAT3 inhibitors with anticancer properties. Recent studies have shown aldehyde dehydrogenase 1 (ALDH1) to be a marker of cancer stem cells (CSC) in HNSCC. The aim of this study was to investigate the therapeutic effect of cucurbitacin I in HNSCC-derived CSCs. Using immunohistochemical analysis, we firstly showed that CD44, ALDH1, and phosphorylated STAT3 (p-STAT3) were higher in high-grade HNSCCs, and that triple positivity for CD44/ALDH1/p-STAT3 indicated a worse prognosis for HNSCC patients. Secondly, CD44

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Section: Discussionmentioning

confidence: 99%

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Chen

Huang

et al. 2010

Molecular Cancer Therapeutics

123

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“…Kweon et al (2010) showed that resveratrol, a popular stilbenoid from red wine, facilitated the cellular concentration of DOX in AML cells via downregulation of the expression of the ABCC1 transporter. Cucurbitacin E, a plant steroid, inhibited DOX efflux and increased (Sadzuka et al, 2010). Dibenzocyclooctadiene lignans, polyphenolic substances, potentiated the cytotoxic effect of DOX in a DOX-resistant lung cancer cell line by increasing the DOX accumulation inside the cells (Slaninova et al, 2009).…”

Section: Natural Substances As Inhibitors Of Efflux Transportersmentioning

confidence: 99%

Possibilities to increase the effectiveness of doxorubicin in cancer cells killing

Hanušová¹,

Boušová²,

Skálová³

2011

Drug Metabolism Reviews

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Anthracycline antibiotic doxorubicin (DOX) belongs among the most important antineoplastics used in cancer therapy. Unfortunately, its cytostatic effect in therapeutic doses is frequently insufficient; but the use of higher DOX doses is limited by the development of systemic toxicity, especially cardiotoxicity. Therefore, a searching for some possibilities of how to increase DOX efficacy in cancer cells, and minimizing associated toxicities to noncancerous tissues, is in the forefront of scientific research. Many approaches are based on altered DOX metabolism. The classical strategies include an enhancing of DOX uptake by cancer cells and/or an activation of DOX prodrug within cancer cells via liposomal encapsulation or conjugation with antibodies, peptides, or synthetic polymers. The diminishing of DOX deactivation, restriction of DOX efflux from cancer cells, decreased antioxidant defense of cancer cells, changes in cell cycle, or modulation of signaling pathways represent newer approaches in increasing DOX toxicity in tumors. Each way has certain advantages and limitations. The aim of this review was not to collect all reported results, but to bring an overview of various approaches and a summary of their principles. Possible advantages, disadvantages, and further perspectives are discussed and evaluated.

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“…Previously, we reported improved DOX-induced antitumor activity using the food components caffeine, theanine, and cucurbitacins. [6][7][8][9][10][11][12][13][14][15] It appeared that these effects were mediated by increased DOX concentration in the tumors, which suppress DOX efflux from tumor cells. In contrast, linalool promoted DOX influx into tumor cells and enhanced its activity by acting on the Na + -dependent nucleoside transporter (CNT) 3.…”

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confidence: 99%

Improvements of Doxorubicin-Induced Antitumor Activity and Adverse Reaction by Combined Citrulline

Miyashita

Sadzuka

2014

Biological & Pharmaceutical Bulletin

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Citrulline is an amino acid with antioxidant activity. In this study, effects of citrulline on the adverse effects of doxorubicin (DOX) and DOX-induced antitumor activity were examined. Citrulline significantly inhibited DOX-induced increases in lipid peroxide (LPO) in the heart as adverse reaction. Combined treatment with DOX and citrulline increased DOX levels in tumor cells and enhanced cytotoxicity in vitro by significantly increasing DOX uptake compared with DOX treatment alone. In simultaneous in vivo treatments, combination treatment with DOX and citrulline decreased tumor weight and increased DOX concentrations in tumors. Promotion of DOX uptake by citrulline enhanced the antitumor activity of DOX through the action of energy-independent and Na -independent transporters. This effect of citrulline on DOX influx is identical to that of S-(4-nitrobenzyl)-6-thioinosine, promoting DOX influx through the equilibrative nucleoside transporter 1. Therefore, it is anticipated that citrulline as a food component may enhance DOX efficacy.Key words citrulline; doxorubicin; adverse reaction; antitumor activity; doxorubicin permeability Currently, cancer therapies include surgery, radiation therapy, and chemotherapy, which is appropriate for hematological tumors and general metastases. Among cancer chemotherapies, alkylating agents, antimetabolites, plant alkaloids, antitumor antibiotics platinum compounds, and molecular targeting agents are used. Furthermore, because mechanisms of antitumor agents vary, combined therapies offer clinical potential to enhance antitumor activity and reduce adverse reactions. [1][2][3][4][5] In contrast, while some biochemical modulators without antitumor activity enhance the pharmacological properties of antitumor agents, these can improve the therapeutic indexes or ameliorate adverse reactions by antitumor agents. However, these therapies often enhance antitumor agent induced adverse reactions with the increase in antitumor activity. Hence, developments and discoveries of novel modulators that enhance antitumor activities and reduce adverse reactions to antitumor agents are required.The anthracycline doxorubicin (DOX) is widely used to treat a variety of malignancies, despite the severity of associated adverse reactions, such as cardiotoxicity. Although many studies report enhancement of DOX antitumor activity in tumor cells by direct inhibition of DOX efflux, no agents or combinations have been found to increase the therapeutic index of DOX by expression of these efflux pumps in normal tissues. Previously, we reported improved DOX-induced antitumor activity using the food components caffeine, theanine, and cucurbitacins. [6][7][8][9][10][11][12][13][14][15] It appeared that these effects were mediated by increased DOX concentration in the tumors, which suppress DOX efflux from tumor cells. In contrast, linalool promoted DOX influx into tumor cells and enhanced its activity by acting on the Na + -dependent nucleoside transporter (CNT) 3.16) Furthermore, decreases in DOX levels following...

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Enhancement of doxorubicin concentration in the M5076 ovarian sarcoma cells by cucurbitacin E co-treatment

Cited by 23 publications

References 30 publications

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Cucurbitacin I Suppressed Stem-Like Property and Enhanced Radiation-Induced Apoptosis in Head and Neck Squamous Carcinoma–Derived CD44+ALDH1+ Cells

Possibilities to increase the effectiveness of doxorubicin in cancer cells killing

Improvements of Doxorubicin-Induced Antitumor Activity and Adverse Reaction by Combined Citrulline

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