Pinus densiflora stem bark extract induces breast cancer cell death via oxidative stress mediated lysosomal membrane permeabilization

Lysosomal membrane permeabilization (LMP) causes release of lysosomal proteases into the cytosol and promotes various cell death pathways with activation of other proteins including caspases [1 – 4]. In this study, we investigated the anti-breast cancer potential of Pinus densiflora stem bark extracts using human breast cancer cells, MCF-7. PD6 is one of the bioactive fractions which showed potent cytotoxic effect against MCF-7 cells (IC₅₀ value: 67.83 µg/ml). Mechanistic studies revealed that the cytotoxic effect of PD6 was associated with loss of lysosomal membrane integrity determined by flow cytometry using specific fluorescent tracker dyes and immunoblotting of cytosolic levels of lysosomal proteases cathepsin D and cathepsin B. Subsequently, the annexin V-FITC and PI dual staining assay revealed that PD6 induces apoptosis-like cell death in MCF-7 cells. N-acetylcysteine (NAC), an antioxidant significantly improved the lysosomal membrane integrity and thereby promotes cell viability. This indicates that the lysosomal dysfunction was dependent on oxidative stress in PD6-treated breast cancer cells. Taken together, the results demonstrated that Pinus densiflora stem bark extracts possess potent anticancer effect against human breast cancer.

Acknowledgements: This work was supported by a grant (S211315L010110) from Forest science & Technology projects, Forest Service, Republic of Korea.

Keywords: Pinus densiflora, LMP, MCF-7.

References:

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