Curcumin enhances chemotherapeutic effects and suppresses ANGPTL4 in anoikis-resistant cholangiocarcinoma cells

Tin Tin San; Prasong Khaenam; Virapong Prachayasittikul; Banchob Sripa; Nawapol Kunkeaw; Waraporn Chan-On

doi:10.1016/j.heliyon.2020.e03255

Curcumin enhances chemotherapeutic effects and suppresses ANGPTL4 in anoikis-resistant cholangiocarcinoma cells

Heliyon. 2020 Jan 30;6(1):e03255. doi: 10.1016/j.heliyon.2020.e03255. eCollection 2020 Jan.

Authors

Tin Tin San¹, Prasong Khaenam², Virapong Prachayasittikul³, Banchob Sripa^{4

5}, Nawapol Kunkeaw⁶, Waraporn Chan-On¹

Affiliations

¹ Center for Research and Innovation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand.
² Center for Standardization and Product Validation, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand.
³ Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Nakhon Pathom, 73170, Thailand.
⁴ Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
⁵ WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease); Tropical Disease Research Center, Khon Kaen University, Khon Kaen, 40002, Thailand.
⁶ Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand.

Abstract

Anoikis resistance is a critical feature involved in tumor progression and chemoresistance. Finding approaches to improve the effect of chemotherapy on anoikis-resistant cancer cells is therefore critically important. In this study, we examined the effects of curcumin in anoikis-resistant cholangiocarcinoma (CCA) cells, including HuCCT1 and TFK-1 that were anchorage-independently cultured (AI-cells) using poly (2-hydroxyethyl methacrylate). The AI-CCA cells were treated with curcumin alone or in combination with anti-cancer agents and their responses to each treatment were determined by cell viability assay. Gene expression in AI-cells was determined by quantitative real-time PCR. The potential involvement of angiopoietin-like 4 (ANGPTL4) in anoikis resistance was examined by gene knockdown. It was found that AI-cells tended to resist anti-cancer agents tested, especially AI-HuCCT1, which significantly resisted gemcitabine and suberoylanilide hydroxamic acid (SAHA). Curcumin alone significantly inhibited viability and colony formation of AI-cells. Moreover, curcumin combination significantly enhanced the treatment effect of SAHA on AI-HuCCT1 and AI-TFK-1 cells. Gene expression analysis revealed that ANGPTL4 was markedly upregulated in AI-CCA cells and its knockdown tended to sensitize AI-cells to cell death and treatments. In addition, curcumin treatment decreased phosphorylated STAT3 and expression levels of Mcl-1, HDACs and ANGPTL4. Altogether, these findings reveal the beneficial property of curcumin to potentiate chemotherapeutic effects on anoikis-resistant CCA cells, which might suggest the potential use of curcumin for cancer treatment.

Keywords: Cancer research; Molecular biology; Natural product.