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Licensed Unlicensed Requires Authentication Published by De Gruyter March 6, 2019

Enhanced anti-cancer activity by menthol in HepG2 cells exposed to paclitaxel and vincristine: possible involvement of CYP3A4 downregulation

  • Katsuhito Nagai EMAIL logo , Shuhei Fukuno , Anna Omachi , Sachiko Omotani , Yasutoshi Hatsuda , Michiaki Myotoku and Hiroki Konishi

Abstract

Background

Menthol is widely used as a constituent of functional foods and chemical drugs. In the present study, we investigated changes in the expression of cytochrome P450 isoform CYP3A4mRNA after treating human hepatocellular carcinoma HepG2 cells with menthol. We also examined the effects of pretreatment with menthol on the cytotoxic activity of paclitaxel (PAC) and vincristine (VIN), which are substrates of CYP3A4, in the cells.

Methods

HepG2 cells were maintained in Dulbecco’s Modified Eagle’s Medium. Expression of CYP3A4 was examined by the real-time polymerase chain reaction. Survival rate of HepG2 cells was evaluated by the MTT assay.

Results

The gene expression level of CYP3A4 in HepG2 cells was significantly reduced by treatment with menthol for 1 day. The viability of HepG2 cells was not affected by treatment with menthol alone once a day for two consecutive days. The degree of reduction in cell viability by PAC or VIN in HepG2 cells was significantly increased by menthol treatment for 24 h prior to exposure to these anti-cancer drugs.

Conclusions

These results demonstrate that menthol enhanced the anti-tumor effects of PAC and VIN through the downregulation of CYP3A4 in HepG2 cells without exerting cytotoxic activity.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s)played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2018-09-14
Accepted: 2018-11-15
Published Online: 2019-03-06

©2019 Walter de Gruyter GmbH, Berlin/Boston

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