Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity

Miyashita, Michiko; Sadzuka, Yasuyuki

doi:10.1016/j.fct.2012.11.035

Cited by 40 publications

(33 citation statements)

References 30 publications

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“…In previous study, combined treatment with DOX and linalool (0.1 µM) significantly increased DOX cytotoxicity in vitro and DOX combined with linalool (1.0 mg/kg/d) enhanced the antitumor activity in vivo. 16) In this study, combined treatment with DOX and 10 µM citrulline significantly increased DOX cytotoxicity in vitro. Therefore, citrulline was administered at 100 mg/kg/d in vivo.…”

Section: Discussionmentioning

confidence: 57%

“…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 combined therapy with these dietary modulators in normal tissues could reduce adverse reactions to DOX, leading to enhanced antitumor activity, reduced patient burden, and increased quality of life.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 57%

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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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“…Maeda and collaborators [190] demonstrated that linalool significantly suppressed HL60 cell proliferation, induced apoptosis, and promoted cell differentiation. The effect of linalool on doxorubicin-induced antitumor activity was evaluated by Miyashita and Sadzuca [191]. …”

Section: Introductionmentioning

confidence: 99%

Antitumor Activity of Monoterpenes Found in Essential Oils

Sobral

Xavier

Lima

et al. 2014

The Scientific World Journal

213

142

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Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.

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“…It has been reported that linalool exhibits antiproliferative activity against certain solid tumor cells, such as melanoma, renal adenocarcinoma [105] and HepG2 cells [106]. Particularly, linalool induced apoptosis in human leukemia cells without affecting growth of normal hematopoietic cells [107] and it was an effective doxorubicin modulator [108].…”

Section: Salvia Officinalis Salvia Officinalis L (Common Sagementioning

confidence: 99%

Biological effects of four frequently used medicinal plants of Lamiaceae

Srančíková¹,

Horvathova²,

Kozics³

2014

neo

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Cancer is one of the leading causes of death characterized by uncontrolled growth and spread of cancer cells. There are several hundred thousands of new cases of cancer worldwide. Clinical oncology is still challenged by toxicity and side effects of multimodal therapy strategies in which it is associated with poor prognosis for patients. There is an urgent necessity to develop novel therapy strategies and to utilize preventive potential of natural compounds. As the majority of anticancer drugs are of natural origin, natural products represent a valuable source for the identification and development of novel treatment options and chemopreventive mechanisms for cancer. This review is focused on the summary of published knowledges on the antioxidant and potential chemopreventive effects of biologically active substances present in the extracts of four plants of the family Lamiaceae (sage, thyme, rosemary and lavander) in different animal and in vitro systems. It is assumed that the chemopreventive and chemotherapeutic potential of natural compounds is the result of a combined action of several mechanisms.

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Effect of linalool as a component of Humulus lupulus on doxorubicin-induced antitumor activity

Cited by 40 publications

References 30 publications

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

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

Antitumor Activity of Monoterpenes Found in Essential Oils

Biological effects of four frequently used medicinal plants of Lamiaceae

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