Antigrowth and Apoptosis Inducing Effects of Hypericum Olympicum L . and Hypericum Adenotrichum Spach. on Lung Cancer Cells In Vitro : Involvement of DNA Damage

Abstract

Hypericum species are used in different folk medicines and screened for their biological activity including cancer. We, therefore, evaluated the possible cytotoxic/ apoptotic and genotoxic activities of Hypericum adenotrichum Spach. and Hypericum olympicum L. Antigrowth effect was screened in human lung cancer cell lines (A549 and PC3) by the ATP viability assay, while genotoxic activity was performed using the Comet assay. Histological and biochemical methods were utilized to elucidate the cell death mode. The results indicate that the crude methanol extracts of H. olympicum L. and H. adenotrichum have both antigrowth/ cytotoxic and genotoxic activities on these cells in a dose dependent manner. These extracts clearly induced apoptosis in PC3 lung cancer cell lines. In this study, we report for the first time that the H. olympicum and H. adenotrichum exhibits potential cytotoxic and genotoxic activities in lung cancer cells as well as the apoptosis-inducing roles through DNA damage in PC3 cells. PRACTICAL APPLICATIONSMedicinal plants are used in traditional medicine worldwide and several have been screened for their anticancer properties, we evaluated the possible cytotoxic and genotoxic activities of the Hypericum adenotrichum and Hypericum olympicum, which are still used in Turkish folk medicine. H. adenotrichum Spach., an endemic species in Turkey, and H. olympicum L., which are known as "kantaron" and used traditionally for their wound healing and antiseptic properties. It was found that Hypericum species showed a significant growth-inhibiting effect on human lung cancer cells and induced apoptosis-like cell death by DNA damage in PC3 lung cancer cells. These species may have a potential as anticancer agents and inspire to new improvements for medicinal chemistry.

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

“…Also, a growth inhibitory and programmed cell death inducing effects of H. olympicum subsp. olympicum extract in lung cancer cells was previously reported by our research group (Aztopal et al, 2016).…”

“…Uludag region in Bursa, Turkey. A methanolic extract from 30 g of the trunk and flowers of this plant was prepared by utilizing a Soxhlet apparatus as previously described (Aztopal et al, 2016). The sample was lyophilized and kept at -20 °C for further use.…”

Nonapoptotic cell death induced by Hypericum species on cancer cells

“…Recently, Li et al [14] examined that Hypericum ascyron extract has cytotoxic activity against different cancer cell lines. In our previously study, we demonstrated that the extract of Hypericum adenotrichum and Hypericum olympicum have cytotoxic activity on lung cancer cells by inducing apoptosis [19]. In this study, we showed that HAE and HOE exhibited significant anti-growth activity against human hepatoma (Hep3B) and rat glioma (C6) cell lines in a dose dependent manner.…”

“…These results demonstrated that the cells dying by necrosis after the treatment with HAE and HOE. In our previously studies, we found that HAE and HOE have cytotoxic effects by inducing apoptosis in human breast and lung cancer cells [19,20]. In another study, Ozmen et al [39] reported that petroleum ether extract of Hypericum adenotrichum induced apoptosis through on caspase 3 activation and PARP cleavage in HL-60 cells.…”

“…Collection, authentication and extraction of Hypericum olympicum and Hypericum adenotrichum were described previously [19]. The crude extracts of Hypericum adenotrichum and Hypericum olympicum were dissolved in DMSO as a stock solution (100 mg/ml) and stored at -20ºC.…”