title: A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid.
abstract: Transferrin receptor (TfR) has been shown to be significantly overexpressed in different types of cancers. We discovered TfR as a target for gambogic acid (GA), used in traditional Chinese medicine and a previously undiscovered link between TfR and the rapid activation of apoptosis. The binding site of GA on TfR is independent of the transferrin binding site, and it appears that GA potentially inhibits TfR internalization. Down-regulation of TfR by RNA interference decreases sensitivity to GA-induced apoptosis, further supporting TfR as the primary GA receptor. In summary, GA binding to TfR induces a unique signal leading to rapid apoptosis of tumor cells. These results suggest that GA may provide an additional approach for targeting the TfR and its use in cancer therapy.
authors.affiliation: Maxim Pharmaceuticals, Inc., 6650 Nancy Ridge Drive, San Diego, CA 92121, USA. skasibhatla@maxim.com
authors.forename: Shailaja
authors.initials: S
authors.lastname: Kasibhatla
authors.forename: Katayoun A
authors.initials: KA
authors.lastname: Jessen
authors.forename: Sergei
authors.initials: S
authors.lastname: Maliartchouk
authors.forename: Jean Yu
authors.initials: JY
authors.lastname: Wang
authors.forename: Nicole M
authors.initials: NM
authors.lastname: English
authors.forename: John
authors.initials: J
authors.lastname: Drewe
authors.forename: Ling
authors.initials: L
authors.lastname: Qiu
authors.forename: Shannon P
authors.initials: SP
authors.lastname: Archer
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Ponce
authors.forename: Nilantha
authors.initials: N
authors.lastname: Sirisoma
authors.forename: Songchun
authors.initials: S
authors.lastname: Jiang
authors.forename: Han-Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Gehlsen
authors.forename: Sui Xiong
authors.initials: SX
authors.lastname: Cai
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Green
authors.forename: Ben
authors.initials: B
authors.lastname: Tseng
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D017931:DNA Primers; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009369:Neoplasms / Q000188:drug therapy*; D034622:RNA Interference; D011990:Receptors, Transferrin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044004:Xanthones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D011990:Receptors, Transferrin; D044004:Xanthones; C052659:gambogic acid