Effects of triptolide from Tripterygium wilfordii on ERalpha and p53 expression in two human breast cancer cell lines.
The aim of the study was to discover possible differential cytotoxicity of triptolide towards estrogen-sensitive MCF-7 versus estrogen-insensitive MDA-MB-231 human breast cancer cells. Considering that MCF-7 cells express functional Estrogen receptor alpha (ERalpha) and wild-type p53, whereas MDA-MB-231 cells which are ERalpha-negative express mutant p53, the anti-proliferation effect of triptolide on MCF-7 and MDA-MB-231 cells were examined, the apoptotic effect and cell cycle arrest caused by triptolide were investigated, ERalpha and p53 expression were also observed in this paper. The results showed that the anti-proliferation effects were induced by triptolide in both cell lines. But the value of IC(50) in MCF-7 cells for its anti-proliferation effect was about one tenth of that in MDA-MB-231 cells, which indicated that the effect is more potent in MCF-7 cells. Condensed chromatin or fragmented nuclei could be found in MCF-7 cells treated with only 40nM triptolide but in MDA-MB-231 cells they couldn't be observed until the concentration reached to 400nM. Triptolide induced significant S cell cycle arrest along with the presence of sub-G0/G1 peak in MDA-MB-231 cells, whereas there was only slightly S cell cycle arrest on cell cycle distribution in MCF-7 cells. The role of p53 in two breast cancer cells was examined, the results showed that the mutant p53 in MDA-MB-231 cells was suppressed and the wild-type p53 in MCF-7 was increased. Moreover, triptolide could down regulate the expression of ERalpha in MCF-7 cells. The results showed that triptolide is much more sensitive to ERalpha-positive MCF-7 cells than to ERalpha-negative MDA-MB-231 cells, and the sensitivity is significantly associated with the ERalpha and p53 status.
Liu
Jing
J
National Center of Drug Screening, China Pharmaceutical University, 1 Shennong Road, Nanjing 210038, China.
Jiang
Zhenzhou
Z
Xiao
Jingwei
J
Zhang
Yun
Y
Lin
Sensen
S
Duan
Weigang
W
Yao
Jincheng
J
Liu
Chunhui
C
Huang
Xin
X
Wang
Tao
T
Liang
Zhongliang
Z
Wang
Rongrong
R
Zhang
Shuang
S
Zhang
Luyong
L
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D053144:Cell Nucleus Shape / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D010616:Phenanthrenes / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology*; D029757:Tripterygium / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D004224:Diterpenes; D004852:Epoxy Compounds; D047628:Estrogen Receptor alpha; D010616:Phenanthrenes; D010936:Plant Extracts; D016159:Tumor Suppressor Protein p53; C001899:triptolide