Ubat Kanser: cucurbitacin B
Inhibition of Wnt
signaling by cucurbitacin B in breast cancer cells: reduction of Wnt-associated
proteins and reduced translocation of galectin-3-mediated β-catenin to the
nucleus.
Source ; Mahidol University, Bangkok, Thailand.
Abstract
The
cucurbitacins are tetracyclic triterpenes found in plants of the family
Cucurbitaceae. Cucurbitacins have been shown to have anti-cancer and
anti-inflamatory activities. We investigated the anti-cancer activity of
cucurbitacin B extracted from Thai medicinal plant Trichosanthes cucumerina
Linn. Cell viability was assessed by MTT
(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Results indicated
that cucurbitacin B from T. cucumerina Linn. has a cytotoxic effect on breast
cancer cell lines SKBR-3 and MCF-7 with an IC50 of 4.60 and 88.75 µg/ml, respectively. Growth
inhibition was attributed to G2/M phase arrest and apoptosis. Cyclin D1, c-Myc,
and β-catenin expression levels were reduced. Western blot analysis showed
increased PARP cleavage and decreased Wnt-associated signaling molecules
β-catenin, galectin-3, cyclin D1 and c-Myc, and corresponding changes in
phosphorylated GSK-3β levels. Cucurbitacin B treatment inhibited translocation
to the nucleus of β-catenin and galectin-3. The depletion of β-catenin and
galectin-3 in the nucleus was confirmed by cellular protein fractionation.
T-cell factor (TCF)/lymphoid enhancer factor (LEF)-dependent transcriptional
activity was disrupted in cucurbitacin B treated cells as tested by a TCF
reporter assay. The relative luciferase activity was reduced when we treated
cells with cucurbitacin B compound for 24 h. Our data suggest that
cucurbitacin B may in part induce apoptosis and exert growth inhibitory effect
via interruption the Wnt signaling.
Inhibitory
effects of cucurbitacin B on laryngeal squamous cell carcinoma.
Source
Department of Otolaryngology, Clinical
Medical School of Hangzhou Normal University, Hangzhou 310015, Zhejiang,
People's Republic of China.
Abstract
Cucurbitacins are
compounds isolated from various plant families, which have been used as folk
medicines for centuries in countries such as India and China because of their
wide spectrum of pharmacological activities such as cytotoxic,
anti-inflammatory, and anticancer effects. Accumulated evidences have shown
that cucurbitacin B inhibits the growth of numerous human cancer cell lines and
tumor xenografts. To determine whether cucurbitacin B can inhibit the growth of
laryngeal squamous cell carcinoma, in the present study we investigated the
antitumor effect of cucurbitacin B on Hep-2 cells. Hep-2 cells were treated
with different concentrations of cucurbitacin B for different time. Cell
proliferation, cell cycle distribution, and cell apoptosis were evaluated using
MTT assay, flow cytometry, and fluorescent microscopy. It was found that
cucurbitacin B exhibited significant efficacy in growth inhibition, cell cycle
arrest at G2/M phase, and apoptosis induction in a dose- and time-dependent
manner. Measuring the modulation of regulators in the cell cycle, apoptosis and
signal transductions by Western blot analysis showed that the effect of
cucurbitacin B was due to suppression of the expression of p-STAT3, Bcl-2, and
cyclin B1. Moreover, in vivo studies were performed in a mouse xenograft model,
where cucurbitacin B inhibited tumor growth in a dose-dependent manner. In
conclusion, the antitumor effect of cucurbitacin B on Hep-2 cells was due to
the induction of cell cycle arrest as well as apoptosis. The possible
mechanisms underlying the action might be attributed to the suppression of
STAT3 phosphorylation. This investigation suggests a potential clinical
application of cucurbitacin B for the treatment of laryngeal cancer patients.
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