Pro‑apoptotic effects of pycnogenol on HT1080 human fibrosarcoma cells
Kamran Harati1, Pawel Slodnik1, Ansgar Michael Chromik2
1Department of Plastic Surgery, Burn Center, Hand Center, Sarcoma Reference Center, BG‑University Hospital Bergmannsheil, Ruhr‑University Bochum, D‑44789 Bochum, Germany.
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.
Insights
Metabolized Pycnogenol, a pine bark extract, effectively induces apoptosis in human fibrosarcoma cells. This natural compound shows promise as a synergistic therapeutic agent, outperforming its individual constituents in cancer cell death.
Area of Science:
- Oncology
- Pharmacology
- Natural Products
Background:
- Localized fibrosarcomas are primarily treated with surgical resection.
- Metastatic fibrosarcomas present a significant therapeutic challenge, with limited efficacy of conventional chemotherapy (e.g., doxorubicin) in less than 30% of cases.
- Doxorubicin is often unsuitable for elderly patients with cardiac conditions.
Purpose of the Study:
- To investigate the apoptotic effects of Pycnogenol, a well-tolerated pine bark extract, and its constituents on human fibrosarcoma cells (HT1080).
- To evaluate the efficacy of Pycnogenol in inducing cancer cell death, particularly in the context of systemic chemotherapy limitations.
Main Methods:
- Human fibrosarcoma cells (HT1080) were treated with plasma samples from healthy subjects who ingested 300 mg of Pycnogenol.
- Cells were also incubated with Pycnogenol's main constituents: catechin, epicatechin, and taxifolin.
- Cell viability, apoptosis, and necrosis were quantified using flow cytometry, and gene expression was analyzed via RNA microarray.
Main Results:
- Individual constituents (taxifolin, catechin, epicatechin) showed only moderate reduction in HT1080 cell viability.
- Plasma samples from Pycnogenol consumers induced significant apoptotic cell death in HT1080 cells ex vivo.
- RNA microarray analysis revealed Pycnogenol significantly altered the expression of genes involved in apoptotic pathways (e.g., JAK1, DUSP1, RHOA).
Conclusions:
- Metabolized Pycnogenol effectively induces apoptosis in human fibrosarcoma cells.
- Pycnogenol acts synergistically as a mixture, demonstrating greater pro-apoptotic activity than its individual components.
- These findings support further in vivo research into Pycnogenol's potential as a cancer therapeutic.
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