title: Mangiferin enhances the sensitivity of human multiple myeloma cells to anticancer drugs through suppression of the nuclear factor κB pathway.
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.
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Tsubaki
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kino
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Kawamura
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Isoyama
authors.affiliation: Department of Food Science and Nutrition, Kinki University School of Agriculture, Nara, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Itoh
authors.affiliation: Department of Surgery, Kinki University School of Medicine, Osakasayama, Osaka, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Imano
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Genzoh
authors.initials: G
authors.lastname: Tanabe
authors.affiliation: Laboratory of Pharmaceutical Organic Chemistry, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Muraoka
authors.affiliation: Department of Natural Drugs Resources, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Department of Pathology, Kinki University School of Medicine, Osakasayama, Osaka, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Satou
authors.affiliation: Division of Pharmacotherapy, Kinki University School of Pharmacy, Kowakae, Higashi-Osaka, Japan.
authors.forename: Shozo
authors.initials: S
authors.lastname: Nishida
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008558:Melphalan / Q000494:pharmacology; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D044004:Xanthones; C013592:mangiferin; D014750:Vincristine; D004317:Doxorubicin; D008558:Melphalan