Pro‑apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells

Harati,Kamran; Slodnik,Pawel; Chromik,Ansgar Michael; Behr,Björn; Goertz,Ole; Hirsch,Tobias; Kapalschinski,Nicolai; Klein‑Hitpass,Ludger; Kolbenschlag,Jonas; Uhl,Waldemar; Lehnhardt,Marcus; Daigeler,Adrien

doi:10.3892/ijo.2015.2854

Pro‑apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells

Authors:
- Kamran Harati
- Pawel Slodnik
- Ansgar Michael Chromik
- Björn Behr
- Ole Goertz
- Tobias Hirsch
- Nicolai Kapalschinski
- Ludger Klein‑Hitpass
- Jonas Kolbenschlag
- Waldemar Uhl
- Marcus Lehnhardt
- Adrien Daigeler
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Affiliations: Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, Ruhr‑University Bochum, D‑44789 Bochum, Germany, Department of General and Visceral Surgery, St. Josef Hospital, Ruhr‑University Bochum, D‑44791 Bochum, Germany, Institute of Cell Biology (Cancer Research), University of Duisburg‑Essen, D‑45122 Essen, Germany
Published online on: January 27, 2015 https://doi.org/10.3892/ijo.2015.2854
Pages: 1629-1636

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Abstract

Complete surgical resection with clear margins remains the mainstay of therapy for localised fibrosarcomas. Nevertheless, metastatic fibrosarcomas still represent a therapeutic dilemma. Commonly used chemotherapeutic agents like doxorubicin have proven to be effective in <30% of all cases of disseminated fibrosarcoma. Especially elderly patients with cardiac subdisease are not suitable for systemic chemotherapy with doxorubicin. Therefore we tested the apoptotic effects of the well‑tolerated pine bark extract pycnogenol and its constituents on human fibrosarcoma cells (HT1080). Ten healthy subjects (six females, four males, mean age 24.8±6 years) received a single dose of 300 mg pycnogenol orally. Blood plasma samples were obtained before and 6 h after intake of pycnogenol. HT1080 cells were treated with these plasma samples. Additionally, HT1080 were incubated separately with catechin, epicatechin and taxifolin that are known as the main constituents of pycnogenol. Vital, apoptotic and necrotic cells were quantified using flow cytometric analysis. Gene expression was analyzed by RNA microarray. The results showed that single application of taxifolin, catechin and epicatechin reduced cell viability of HT1080 cells only moderately. A single dose of 300 mg pycnogenol given to 10 healthy adults produced plasma samples that led to significant apoptotic cell death ex vivo whereas pycnogenol‑negative serum displayed no apoptotic activity. Microarray analysis revealed remarkable expression changes induced by pycnogenol in a variety of genes, which are involved in different apoptotic pathways of cancer cells [Janus kinase 1 (JAK1), DUSP1, RHOA, laminin γ1 (LAMC1), fibronectin 1 (FN1), catenin α1 (CTNNA1), ITGB1]. In conclusion, metabolised pycnogenol induces apoptosis in human fibrosarcoma cells. Pycnogenol exhibits its pro‑apoptotic activity as a mixture and is more effective than its main constituents catechin, epicatechin and taxifolin indicating that the metabolised components interact synergistically. These results provide experimental support for in vivo trials assessing the effect of the pine bark extract pycnogenol.

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