The recent article by Cui et al. provided for highly stimulating reading.Citation1 Butein may inhibit tumor growth in a number of systemic malignancies.
Butein inhibits growth in hepatocellular carcinomas. It mediates these effects in part by attenuating JNK levels.Citation2 ROS generation is enhanced. Part of this anti-neoplastic effect is also mediated by virtue of butein mediated inhibition of the STAT3 pathway. It also decreases MMP-2 and MMP-9 activity thus further reducing tumor growth.Citation3 ROCK1 and ERK1/2 levels are also decreased. There is increased G2/M phase arrest. It also augments the anti-proliferative activities of chemotherapeutic agents such as doxorubicin. Butein results in NF-κB inhibition as well as up-regulation of DR5. As a result, it accentuates the sensitivity of hepatocellular carcinomas to TRAIL induced apoptosis.Citation4 Chk1 and Chk2 phosphorylation is also increased by butein.Citation5 Similarly, butein decreases tumor growth in pancreatic as well as gastric carcinomas.
Butein also attenuates tumor growth as well as decreases metastasis in breast carcinomas. It mediates this effect by down regulating CXCR4 expression as a result of NF-κB inhibition.Citation6 Ultimately, there is marked decrease in CXCL12-induced migration. This markedly attenuates local invasiveness as well as mitigates tumor metastasis. These effects of butein in breast carcinomas are time dependent. Butein also acts as an aromatase inhibitor.Citation7 It also modulates and interferes with interaction between breast cancer cells and tissue fibroblasts.Citation8
Similarly, butein exerts anti-neoplastic effects in neuroblastomas. It mediates this effect by accentuating ROS levels. It also augments PARP cleavage. Simultaneously it decreases the Bcl-2/Bax ratio.Citation9 The ultimate result is marked accentuation of intra-tumoral apoptosis.
The above examples clearly illustrate the anti-proliferative and pro-apoptotic effects of butein.
Declaration of interest
The author reports no conflicts of interest.
References
- Cui Z, Song E, Hu DN, Chen M, Rosen R, McCormick SA. Butein induces apoptosis in human uveal melanoma cells through mitochondrial apoptosis pathway. Curr Eye Res 2012;37:730–739
- Ma CY, Ji WT, Chueh FS, Yang JS, Chen PY, Yu CC, et al. Butein inhibits the migration and invasion of SK-HEP-1 human hepatocarcinoma cells through suppressing the ERK, JNK, p38, and uPA signaling multiple pathways. J Agric Food Chem 2011;59:9032–9038
- Moon DO, Kim MO, Choi YH, Hyun JW, Chang WY, Kim GY. Butein induces G(2)/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation. Cancer Lett 2010;288:204–213
- Rajendran P, Ong TH, Chen L, Li F, Shanmugam MK, Vali S, et al. Suppression of signal transducer and activator of transcription 3 activation by butein inhibits growth of human hepatocellular carcinoma in vivo. Clin Cancer Res 2011;17:1425–1439
- Moon DO, Kim MO, Choi YH, Kim GY. Butein sensitizes human hepatoma cells to TRAIL-induced apoptosis via extracellular signal-regulated kinase/Sp1-dependent DR5 upregulation and NF-kappaB inactivation. Mol Cancer Ther 2010;9:1583–1595
- Chua AW, Hay HS, Rajendran P, Shanmugam MK, Li F, Bist P, et al. Butein downregulates chemokine receptor CXCR4 expression and function through suppression of NF-kappaB activation in breast and pancreatic tumor cells. Biochem Pharmacol 2010;80:1553–1562
- Wang Y, Chan FL, Chen S, Leung LK. The plant polyphenol butein inhibits testosterone-induced proliferation in breast cancer cells expressing aromatase. Life Sci 2005;77:39–51
- Samoszuk M, Tan J, Chorn G. The chalcone butein from Rhus verniciflua Stokes inhibits clonogenic growth of human breast cancer cells co-cultured with fibroblasts. BMC Complement Altern Med 2005;5:5
- Chen YH, Yeh CW, Lo HC, Su SL, Hseu YC, Hsu LS. Generation of reactive oxygen species mediates butein-induced apoptosis in neuroblastoma cells. Oncol Rep 2012;27:1233–1237