Author(s): Pandey MK, Sung B, Ahn KS, Kunnumakkara AB, Chaturvedi MM, et al.
Gambogic acid (GA), a xanthone derived from the resin of the Garcinia hanburyi, has been recently demonstrated to bind transferrin receptor and exhibit potential anticancer effects through a signaling mechanism that is not fully understood. Because of the critical role of NF-kappaB signaling pathway, we investigated the effects of GA on NF-kappaB-mediated cellular responses and NF-kappaB-regulated gene products in human leukemia cancer cells. Treatment of cells with GA enhanced apoptosis induced by tumor necrosis factor (TNF) and chemotherapeutic agents, inhibited the expression of gene products involved in antiapoptosis (IAP1 and IAP2, Bcl-2, Bcl-x(L), and TRAF1), proliferation (cyclin D1 and c-Myc), invasion (COX-2 and MMP-9), and angiogenesis (VEGF), all of which are known to be regulated by NF-kappaB. GA suppressed NF-kappaB activation induced by various inflammatory agents and carcinogens and this, accompanied by the inhibition of TAK1/TAB1-mediated IKK activation, inhibited IkappaBalpha phosphorylation and degradation, suppressed p65 phosphorylation and nuclear translocation, and finally abrogated NF-kappaB-dependent reporter gene expression. The NF-kappaB activation induced by TNFR1, TRADD, TRAF2, NIK, TAK1/TAB1, and IKKbeta was also inhibited. The effect of GA mediated through transferrin receptor as down-regulation of the receptor by RNA interference reversed its effects on NF-kappaB and apoptosis. Overall our results demonstrate that GA inhibits NF-kappaB signaling pathway and potentiates apoptosis through its interaction with the transferrin receptor.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/17673602
Author(s): Ting AT, Pimentel-Muinos FX, Seed B
Author(s): Reynaert NL, Ckless K, Korn SH, Vos N, Guala AS, et al.
Author(s): Ha KH, Byun MS, Choi J, Jeong J, Lee KJ, et al.
Author(s): Vanhaesebroeck B, Waterfield MD
Author(s): Vivanco I, Sawyers CL
Author(s): Kandel ES, Skeen J, Majewski N, Di Cristofano A, Pandolfi PP, et al.
Author(s): Kandel ES, Hay N
Author(s): Choi JA, Kim JY, Lee JY, Kang CM, Kwon HJ, et al.
Author(s): Kuo PC, Liu HF, Chao JI
Author(s): Ong CS, Tran E, Nguyen TT, Ong CK, Lee SK, et al.
Author(s): Vijayababu MR, Arunkumar A, Kanagaraj P, Arunakaran J
Author(s): Choi EJ, Bae SM, Ahn WS
Author(s): Jung YH, Heo J, Lee YJ, Kwon TK, Kim YH
Author(s): Senthilkumar K, Elumalai P, Arunkumar R, Banudevi S, Gunadharini ND, et al.
Author(s): Senthilkumar K, Arunkumar R, Elumalai P, Sharmila G, Gunadharini DN, et al.
Author(s): Yi L, Su Q
Author(s): Gupta SC, Reuter S, Phromnoi K, Park B, Hema PS, et al.
Author(s): Babykutty S, S PP, J NR, Kumar MA, Nair MS, et al.
Author(s): Kavitha K, Vidya Priyadarsini R, Anitha P, Ramalingam K, Sakthivel R, et al.
Author(s): Lowry OH, Rosebrough NJ, Farr AL, Randall RJ
Author(s): Arunkumar A, Vijayababu MR, Srinivasan N, Aruldhas MM, Arunakaran J
Author(s): Gayathri R, Gunadharini DN, Arunkumar A, Senthilkumar K, Krishnamoorthy G, et al.