Cytotoxic and apoptogenic effect of hypericin, the bioactive component of Hypericum perforatum on the MCF-7 human breast cancer cell line

Abstract

BackgroundBreast cancer is the most prevalent malignancies among the women that have a high mortality. Previous studies demonstrated that hypericin, a bioactive component of Hypericum perforatum have a cytotoxic effect on the malignant cell lines. However, an anti-carcinogenic activity of hypericin on MCF-7 is uncertain. To investigate the cytotoxic effect of hypericin on MCF-7 cells, a human breast adenocarcinoma cell-line, that resistance to chemotherapy.MethodsThe MCF-7 and fibroblast (as normal cell line) were treated with various concentrations of hypericin, and Cisplatin as a positive control for 24 and 48 h. Cytotoxicity activity was measured and confirmed by MTT assay and Trypan blue staining, respectively. In addition, Apoptosis were determined by Annexin V/Propidium Iodide assay. Immunocytochemistry (ICC) analysis for bcl2 and p53 proteins performed to further investigate different expression of these genes in different samples.ResultsBoth cisplatin and the hypericin exhibited a dose-dependent cytotoxic effect in the MCF-7 cell line. Although the LD50 of the hypericin was significantly lower when compared to cispaltin (5 vs. 20 μg/ml), it continued to decrease the growth rate of the MCF-7 cells when tested at higher concentration than LD50. In contrast, cisplatine, at higher concentration than LD50, completely inhibited the growth of the MCF-7 in 48 h. Regarding Annexin V/Propidium results, treatment of MCF-7 cells with LD50 concentration of cisplatin and hypericin showed 60 and 52 % apoptosis in 24 h, respectively. ICC analysis for bcl2 and p53 also confirmed our results; in treated samples for the dose of LD50 in 24 and 48 h of cisplatin and hypercin, more cells expressed p53 (guardian of cells in front of tumor formation/progression) and less expressed bcl2 (which has anti apoptotic activity) compared to untreated samples.ConclusionsConsidering that hypericin showed to be cytotoxic, it seems to be a chemopreventive agent and a good candidate for antineoplastic drug development.

Distinct Hypericum perforatum L. total extracts exert different antitumour activity on erythroleukemic K562 cells

“…This effect was independent from hypericins, a class of compounds peculiar of this species. In fact, not photo activated hypericin, alone, taken as reference, was not active in our model, although this subject is still under debate (Hostanska, Reichling, Bommer, Weber, & Saller, 2003;Mirmalek et al, 2016;Schwarz, Kisselev, & Roots, 2003).…”

A Stilbenoid Isorhapontigenin as a Potential Anti-Cancer Agent against Breast Cancer through Inhibiting Sphingosine Kinases/Tubulin Stabilization

“…Once the cell confluence was almost 80-90%, cells were subcultured and maintained. Cells were seeded in 96-or 24-well plates with the desired quantity of cells, as per the experimental protocol [42]. After 24 h, seeded cells were treated with the desired compounds and incubated for the indicated time points depending upon the different experiments.…”

Toxicity assessment of Hypericum olympicum subsp. olympicum L. on human lymphocytes and breast cancer cell lines

“…It has been shown that either whole extract or some biologically active constituents of different Hypericum species exhibit anti-inflammatory, anti-microbial, anti-depressant, anti-oxidant and anti-tumor activity (Bender et al, 2018;Ozkan et al, 2018;Tian et al, 2014;Zorzetto et al, 2015). Furthermore, cytotoxic, genotoxic and apoptosis-inducing effects against different cancer cells have also been highlighted in recent studies (Keskin et al, 2017;Mirmalek et al, 2015;Sarimahmut et al, 2016;Sousa et al, 2015). The most renowned Hypericum species, Hypericum perforatum (St. John's Wort), is extensively studied and utilized in traditional medicine due to its antidepressant activity and in burn-wound-healing with many pharmacological properties due to its active ingredients hypericin, hyperforin and other flavonoid compounds (Barnes et al, 2001;Baytop, 1984).…”