000 06034nas a2200469 a 4500
005 20260818112538.0
008 130214s2011 th uu|m rtt 0| a1eng d
035 _a.b12114972
099 9 _aAIT Diss. no.EV-11-04
100 0 _aPrisna Pianjing
245 1 0 _aEstrogenic activities of sesame lignans and their metabolites :
_binteractive effect with cadmium in human breast cancer cell lines
260 _aPathum Thani, Thailand :
_bAsian Institute of Technology,
_c2011
300 _a91 leaves :
_bill. (some col.)
490 1 _aDissertation ;
_vno. EV-11-04
500 _aA dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Environmental Engineering and Management Inter-University Program on Environmental Toxicology, Technology and Management, School of Environment, Resources and Development
502 _aThesis (Ph.D.) - Asian Institute of Technology - Chulabhorn Research Institute - Mahidol University, 2011
520 _aThe estrogenic activities of sesame lignans and their metabolites were investigated by using a viability assay and estrogen response elements (ERE) rep01ier system on the different levels of estrogen in cultured media. Hormone-dependent human breast cancer T47D cells and the cells stably transfected with ERE-luciferase reporter system T47DKBluc cells were utilized. Depending on levels of E2, sesame lignans and their metabolites exhibited different effects on the viability of T47D-KBluc cells. In the absence of estrogen, the trend of induction of cell growth was observed, whereas in the presence of estrogen, cytotoxic effect was evidenced. The ERE luciferase rep01ier assay in T47DKB1uc cells shows that, sesame lignans and their metabolites induced ERE activation. Among tested compounds, sesamol possessed the highest ERE activation prope1iy while ED showed no effect. All tested compounds exhibited lower levels of ERE activation than that of estradiol (E2) activation, suggesting that the tested compounds possess weak estrogenic effect. The antiestogen ICI 182 780 significantly decreased ERE activation induced by the te<ited compounds indicating the involvement of ER in their ERE activations. When 10 æM of tested compounds were co-incubated with various concentrations of E2 (10" 12-10"6 M), all tested compounds decreased the maximum responses of E2-ERE activations indicating that the tested compounds exhibit antiestrogenic effects in the presence of E2. Interestingly, tested compounds inhibited E2- ERE induction by a downward-shift of the E2-ERE dose-response curve. This was different from the inhibitory effects of tamoxifen and ICI 182 780 which showed the parallel-shift of E2-ERE dose-response curves without decreasing the maximum responses of E2-ERE induction. These results suggested that sesame lignans and their metabolites exhibited a non-competitive antagonistic property on E2-ERE activation. Real-time RTPCR studies showed that sesame lignans and their metabolites can induce estrogen targeted pS2 and progesterone receptor gene, suggesting their ERE induction abilities were functional. Cadmium at concentration 5 æM enhanced E2-ERE activation while sesamol, the most prominent ERE activator, could attenuate this response. When T47D cells were treated with cadmium, sesamol, or cadmium plus sesamol in the presence of E2, the results showed that cadmium increased expression of ERa while sesamol or sesamol plus cadmium decreased this expression, suggesting that sesamol may decrease cadmiuminduced estrogenic activity by modulating through ER. In particular, cadmium and sesamol induced alteration of ER expression in cytoplasm; whereas the expression of ERa in nucleus did not change when compared to control. Cadmium induced ERa expression in cytoplasm without the alteration of ERP expression when compared to control. Sesamol or sesamol plus cadmium decreased the expression of ERa while sesamol alone increased the expression of ERP in cytoplasm suggesting that in the presence of E2, sesamol preferentially interacted with ERa and ERP in cytoplasm. Sesamol may decrease cadmium-induced estrogenic activity by modulating ERa in cytoplasm. Fmihermore, these results indicate that sesame lignans and their metabolites possess estrogenic/antiestrogenic effect on ERE activation in human breast cancer cells in accordance with the E2 levels. In the presence of E2, sesamol, a metabolite form of sesamolin, may have the potential for prevention of cadmium- induced estrogenic effect in human breast cancer cells.
650 0 _aSeseme
650 0 _aEstrogen
650 0 _aBreast
_xCancer
700 1 _aJutamaad Satayavivad,
_eChairperson
700 1 _aApinya Thiantanawat,
_eCo-Chairperson
700 0 _aPreeda Pakpian,
_eExamination Committee
700 1 _aNuchanart Rangkadilok,
_eExamination committee
700 1 _aBung-om SripanidkulchaiIeExamination committee
710 2 _aChulabhorn Research Institute/Mahidol University/ AIT Fellowship (CRI-MU-AIT), Scholarship donor
810 2 _aAsian Institute of Technology.
_tDissertation ;
_vno. EV-11-04
856 _3Full-Text
_uhttp://203.159.5.9/ait-thesis/detail.php?q=B11290
907 _a.b12114972
_bmnait
_cz
902 _a240403
998 _b0
_c130214
_dm
_ea
_fz
_g0
962 _a000:001:PDF:b1211497:000863:0:0:0:0:0:0
_tAbstract
_vn
945 _lmnait
945 _lmnait
945 _lmnarc
942 _c20
942 _c40
909 _aBarcode : 30050120553762
_bCREATED : 2013-02-14
_cRECORD # : i12725158
_dLPATRON : 0
_eLCHKIN : -
_f# RENEWALS : 0
_g# OVERDUE : 0
_hIUSE3 : 0
_iTOT CHKOUT : 0
_jTOT RENEW : 0
909 _aBarcode : 30050120553754
_bCREATED : 2013-02-14
_cRECORD # : i1272516x
_dLPATRON : 1015494
_eLCHKIN : 2015-04-02
_f# RENEWALS : 0
_g# OVERDUE : 0
_hIUSE3 : 0
_iTOT CHKOUT : 1
_jTOT RENEW : 0
909 _aBarcode : 30050160004056
_bCREATED : 2016-09-02
_cRECORD # : i12879307
_dLPATRON : 0
_eLCHKIN : -
_f# RENEWALS : 0
_g# OVERDUE : 0
_hIUSE3 : 0
_iTOT CHKOUT : 0
_jTOT RENEW : 0
999 _c40329
_d40329