Abstract
Background: Breast cancer is the major cause of death from cancer among women around the world. Given the drug resistance in
the treatment of this disease, it is very important to identify new therapies and anticancer drugs. Many studies demonstrated that
hypericin could induce apoptosis in different cancer cell lines; however, the underlying mechanism is not well understood yet.
Therefore, this study aimed to evaluate the anticancer effect of hypericin in two breast cancer cell lines, one with wild type P53
and the other with mutant P53.
Methods: In this study, the MDA-MB-231 and MDA-MB-175-VII cell lines were treated with different concentrations of hypericin
for 24 and 48 hours. The measurement of cell death was performed by MTT assay. The cell apoptosis rate was measured using
annexin V/propidium iodide assay through flow cytometry. The level of expression in P21 and P53 genes was evaluated by real
time PCR. Immunocytochemistry (ICC) analysis was performed for P21 (direct target for P53 protein) to confirm the results.
Results: The results showed that hypericin could have dose-dependent cytotoxic effects on the MDA-MB-231 and MDA-MB-175-
VII cell lines, and its cytotoxicity is much higher in the latter cells. According to flow cytometry results, 86% of MDA-MB-175-VII
cells underwent apoptosis with IC50 dose of hypericin for MDA-MB-231 cells after 24 hours. Moreover, after 24 hours of exposure
to hypericin with MDA- MB-231 IC50 concentration, the expression of P53 and P21 genes upregulated in MDA-MB-175-VII much
more than MDA-MB-231 when both cell lines were treated with 24 hours IC50 dose of MDA-MB-231. The ICC analysis on P21
confirmed that by treating both cell lines with MDA-MB-231 IC50 dose of hypericin for 24 hours, this protein is overexpressed
much more in MDA-MB-175-VII cells.
Conclusion: The results of this study demonstrated that hypericin’s apoptotic and cytotoxic effects on cancer cells may be mediated
via P53 overexpression, cell cycle arrest and the subsequent apoptosis. Therefore, it is of great importance to consider that
hypericin would have better impact on cells or tumors with wild type P53.