A role for transferrin receptor in triggering apoptosis when targeted with gambogic acid.
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.
Kasibhatla
Shailaja
S
Maxim Pharmaceuticals, Inc., 6650 Nancy Ridge Drive, San Diego, CA 92121, USA. skasibhatla@maxim.com
Jessen
Katayoun A
KA
Maliartchouk
Sergei
S
Wang
Jean Yu
JY
English
Nicole M
NM
Drewe
John
J
Qiu
Ling
L
Archer
Shannon P
SP
Ponce
Anthony E
AE
Sirisoma
Nilantha
N
Jiang
Songchun
S
Zhang
Han-Zhong
HZ
Gehlsen
Kurt R
KR
Cai
Sui Xiong
SX
Green
Douglas R
DR
Tseng
Ben
B
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
D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D011990:Receptors, Transferrin; D044004:Xanthones; C052659:gambogic acid