4',6'-Dimethoxy-2'-hydroxychalcone

Description

Flavokawain B is a natural chalcone first isolated from extracts of kava roots. It induces apoptosis in androgen receptor-negative, hormone-refractory prostate cancer cell lines (IC₅₀s = 32, 48, 6.2, and 3.9 μM for LAPC4, LNCaP, PC-3, and DU145 cells, respectively, treated for 48 hours), with increased expression of the proapoptotic protein Bim. Flavokawain B increases Bim expression and inhibits growth of DU145 xenografts in mice. It also increases Bim expression, promotes apoptosis, and induces cell cycle arrest in uterine leiomyosarcoma cells. However, flavokawain B is hepatotoxic, triggering oxidative stress, inhibiting NF-κB signaling, and activating MAPK pathways, culminating in HepG2 and L-02 cell death (LD₅₀s = 15 and 32 μM, respectively).

Chemical Properties

Pale yellow powder, soluble in organic solvents such as methanol, ethanol, and DMSO, derived from the rhizome of Piper methysticum Forst.

Uses

Flavokavain B is a secondary metabolite of the kava plant (Piper methysticum Forst. f., Piperaceae, which has anticancer properties and demonstrated oral efficacy in murine cancer models. Futhermore, it also has suspected roles in rare cases of kava-induced hepatotoxicity. In addition, it is a potential candidate for the development of novel antifungal phytotherapic products.

Definition

ChEBI: Flavokawain B is a member of the class of chalcones that consists of trans-chalcone substituted by hydroxy group at positions 2' and methoxy groups at positions 4' and 6'. Isolated from Piper methysticum and Piper rusbyi, it exhibits antileishmanial, anti-inflammatory and antineoplastic activities. It has a role as a metabolite, an antileishmanial agent, an anti-inflammatory agent, an apoptosis inducer and an antineoplastic agent. It is a member of chalcones, a dimethoxybenzene and a member of phenols. It is functionally related to a trans-chalcone.

in vivo

References

[1] De Souza, F.I., Zumiotti, A.V., and Da Silva, C.F. Neuregulins 1-α and 1-β on the regeneration the peripheral nerves[J]. Acta Ortop Bras.
[2] RAMEZ N. ESKANDER. Flavokawain B, a novel, naturally occurring chalcone, exhibits robust apoptotic effects and induces G2/M arrest of a uterine leiomyosarcoma cell line[J]. Journal of Obstetrics and Gynaecology Research, 2012, 38 8: 1086-1094. DOI: 10.1111/j.1447-0756.2011.01841.x
[3] PING ZHOU. Flavokawain B, the hepatotoxic constituent from kava root, induces GSH-sensitive oxidative stress through modulation of IKK/NF-κB and MAPK signaling pathways[J]. FASEB Journal, 2010, 24 12: 4722-4732. DOI: 10.1096/fj.10.163311