Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer drugs through suppression of the nuclear factor κB pathway

Takeda,Tomoya; Tsubaki,Masanobu; Kino,Toshiki; Kawamura,Ayako; Isoyama,Shota; Itoh,Tatsuki; Imano,Motohiro; Tanabe,Genzoh; Muraoka,Osamu; Matsuda,Hideaki; Satou,Takao; Nishida,Shozo

doi:10.3892/ijo.2016.3470

Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer drugs through suppression of the nuclear factor κB pathway

Authors:
- Tomoya Takeda
- Masanobu Tsubaki
- Toshiki Kino
- Ayako Kawamura
- Shota Isoyama
- Tatsuki Itoh
- Motohiro Imano
- Genzoh Tanabe
- Osamu Muraoka
- Hideaki Matsuda
- Takao Satou
- Shozo Nishida
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Affiliations: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan, Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Japan, Department of Surgery, Kinki University School of Medicine, Osakasayama, Osaka, Japan, Laboratory of Pharmaceutical Organic Chemistry, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan, Department of Natural Drugs Resources, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan, Department of Pathology, Kinki University School of Medicine, Osakasayama, Osaka, Japan
Published online on: April 1, 2016 https://doi.org/10.3892/ijo.2016.3470
Pages: 2704-2712

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Abstract

Multiple myeloma (MM) is still an incurable hematological malignancy with a 5-year survival rate of ~35%, despite the use of various treatment options. The nuclear factor κB (NF-κB) pathway plays a crucial role in the pathogenesis of MM. Thus, inhibition of the NF-κB pathway is a potential target for the treatment of MM. In a previous study, we showed that mangiferin suppressed the nuclear translocation of NF-κB. However, the treatment of MM involves a combination of two or three drugs. In this study, we examined the effect of the combination of mangiferin and conventional anticancer drugs in an MM cell line. We showed that the combination of mangiferin and an anticancer drug decreased the viability of MM cell lines in comparison with each drug used separately. The decrease in the combination of mangiferin and an anticancer drug induced cell viability was attributed to increase the expression of p53 and Noxa and decreases the expression of XIAP, survivin, and Bcl-xL proteins via inhibition of NF-κB pathway. In addition, the combination treatment caused the induction of apoptosis, activation of caspase-3 and the accumulation of the cells in the sub-G1 phase of the cell cycle. Our findings suggest that the combination of mangiferin and an anticancer drug could be used as a new regime for the treatment of MM.

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