Yuehchukene, a bis-indole alkaloid, and cyclophosphamide are active in breast cancer in vitro.
Yuehchukene (YCK) is a novel bis-indole alkaloid with weak estrogenic activity. Biochemical studies showed that YCK could attenuate estrogenic action. In this study, the response of MCF-7, an estrogen-receptor-positive breast cancer cell line, under different combinations of estradiol, cyclophosphamide and YCK, was tested. From the dose-response curve, we discovered that 10(-2) M cyclophosphamide, even in its so-called 'bio-inert' form, could inhibit MCF-7 cell growth. However, the cytotoxic effect of cyclophosphamide was lost by reducing its concentration to approximately 1 x 10(-3) M. On the other hand, a low concentration ( approximately 10(-8)-10(-9) M) of YCK was found to potentiate the cytotoxic effect of cyclophosphamide on the MCF-7 cell line. Such an effect was absent in the estrogen-receptor-negative cell line MDA-MB-231. These findings, together with the dual role of a mixed estrogen and anti-estrogen effect, suggested that YCK and cyclophosphamide can be a potential combination in chemo-hormonal therapy for breast cancer.
Leung
T W
TW
Department of Clinical Oncology, Sir Yue-Kong Pao Cancer Centre, The Chinese University of Hong Kong, Hong Kong. waitongleung@chuhk.edu.hk
Cheng
G
G
Chui
C H
CH
Ho
S K
SK
Lau
F Y
FY
Tjong
J K
JK
Poon
T C
TC
Tang
J C
JC
Tse
W C
WC
Cheng
K F
KF
Kong
Y C
YC
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D018906:Antineoplastic Agents, Alkylating; D013778:Tetrazolium Salts; D013844:Thiazoles; D003520:Cyclophosphamide; C047409:yuehchukene; C022616:thiazolyl blue