Abstract
Background:Betulinic acid (BA), a pentacyclic triterpene glycoside extract from guava (Psidium guajava Linn.) leaves, displays a variety of biological activities which exhibit cancer therapeutic properties associated with cancer growth inhibition in various kinds of human cancer cells including brain, breast, colorectal, cervical, lung and prostate gland. However, the effects on human cholangiocarcinoma cells have not previously been reported. Current study, we evaluated the activity of BA against human cholangiocarcinoma (HuCCA) cells. Methods:The cytotoxicity analysis was measured by using MTT assay on HuCCA and BHK-21 cells. Analysis of apoptosis was evaluated by using staining with Hoechst 33342 and quantitative real-time PCR. Results:The BA (50-800 µg/mL) significantly reduced the viability of HuCCA cells in a dose-dependent action with 50% inhibitory concentration (IC50) of 92.45 µg/mL at 24 h. It also induced apoptosis signaling pathway, such as nuclear chromatin condensation and fragmentation. Quantitative real-time PCR analysis demonstrated that BA increased p53, Bax and caspase-3 expression whilst it decreased Bcl-2 expression in the HuCCA cells in a dose dependent manner. Conclusion:BA can inhibit the HuCCA cell viability and induce apoptosis of neoplastic cells. This study indicates that BA has effective treatment for cholangiocarcinoma in vitro. Consequently, BA may be used as a novel therapeutic agent for the treatment of cholangiocarcinoma in the future.
Highlights
Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium, that arise from mutation of the epithelial cells lining the biliary ducts (Fava and Lorenzini, 2011; Gatto et al, 2010)
Cytotoxicity of Betulinic acid (BA) on human cholangiocarcinoma (HuCCA) and BHK-21 After the treatment with BA for 24 h, the cell viability of HuCCA cells were decreased in the dose dependent manner from 50 to 800 μg/mL when compared with control group (Figure 2A)
The current study displays the decrease in HuCCA cell viability in response to the BA which was extracted from guava (Psidium guajava Linn.) leaves
Summary
Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium, that arise from mutation of the epithelial cells lining the biliary ducts (Fava and Lorenzini, 2011; Gatto et al, 2010). It is an important health problem worldwide, especially in many Asian countries (Gores, 2003; Sripa and Pairojkul, 2008; Shin et al, 2010; Sripa et al, 2011). The cancer combination treatments for CCA using chemotherapy and radiotherapy might cause serious side effects (sirica, 2005). Results: The BA (50-800 μg/mL) significantly reduced the viability of HuCCA cells in a dose-dependent action with 50% inhibitory concentration (IC50) of 92.45 μg/mL at 24 h It induced apoptosis signaling pathway, such as nuclear chromatin condensation and fragmentation. BA may be used as a novel therapeutic agent for the treatment of cholangiocarcinoma in the future
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