Tiliacora triandra Leaf Powder Ethanolic Extract in Combination with Cisplatin or Gemcitabine Synergistically Inhibits the Growth of Cholangiocarcinoma Cells In Vitro and in Nude Mouse Xenograft Models

Abstract

Background and Objectives: The treatments of cholangiocarcinoma (CCA) with Cisplatin (Cis) and Gemcitabine (Gem) often cause side effects and drug resistance. This study aimed to investigate the combined effects of Tiliacora triandra leaf powder ethanolic extract (TLPE) and Cis or Gem on CCA cells in vitro and in nude mouse xenografts. Materials and Methods: Antiproliferative activity was evaluated using MTT assay. Drug interaction was studied by Chou-Talalay method. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. Cell cycle and apoptosis regulating proteins were evaluated by western blot analysis. Results:Treatments with Cis or Gem in combination with TLPE significantly inhibited the growth of KKU-M213B and KKU-100 cells compared with single drug treatments. Synergistic drug interactions were observed with the dose reduction of Cis and Gem treatments. The safety of TLPE was demonstrated in vitro by the hemolytic assay. Synergistic combination treatments down-regulated Bcl2 and reduced the ratio of Bcl2/Bax in both CCA cells. TLPE enhanced tumor suppression of both Cis and Gem in nude mouse xenograft models. Combination treatments with Cis and TLPE reduced Cis toxicity, as demonstrated by the enhanced body weight change of the treated mice compared with the treatment with Cis alone. Furthermore, TLPE reduced hepatotoxicity caused by Gem treatment and reduced kidney and spleen toxicities caused by Cis treatment. Conclusion: These findings suggest that TLPE enhances the anticancer activity of Cis and Gem and reduces their toxicity both in vitro and in nude mouse xenograft models.

The Inhibitory Effect of KerraTM, KSTM, and MinozaTM on Human Papillomavirus Infection and Cervical Cancer

“…T. triandra (Colebr.) Diels extracts comprise of many bioactive compounds with anticancer properties, including p-coumaric, ferulic acid, sinapic acid, and phytol [46,47]. The methanolic extract from the leaves of T. triandra (Colebr.)…”

Anticancer Potential of Valencia Peanut (<em>Arachis hypogaea </em>L.) Skin Extract against Cervical Cancer Cells In Vitro and in Nude Mouse Xenograft Models

“…Valencia KK4-type peanut skin ethanolic extract (KK4-PSE) exhibited anticancer activity against HeLa cervical cancer cells in vitro [13], however, its anticancer activity in vivo and its interaction with current anticancer drugs, such as cisplatin and 5-fluorouracil (5-FU), have not yet been explored. Based on the findings that ethanolic extracts of Thai noni juice (TNJ) products and Tiliacora triandra leaf powder enhance the anticancer effect against human cholangiocarcinoma (CCA) cells and reduce toxicity of 5-FU, cisplatin and gemcitabine in nude mouse xenograft models [17,18], we therefore hypothesize that KK4-PSE would enhance anticancer activity of cisplatin or 5-FU against cervical cancer cells both in vitro and in nude mouse xenograft models. In the present study, we explored the anticancer potential of KK4-PSE to inhibit cervical cancer cell growth both in single and combination drug treatments with cisplatin or 5-FU in vitro (HeLa cervical cancer cells) and in vivo (nude mouse xenografts).…”