RESUMEN
BACKGROUND: Drimia maritima (D. maritima) is a plant belonging to the family Asparagaceae, which has been used for the treatment of several ailments including cancer around the world. To our knowledge, there is no comprehensive study about the molecular mechanisms of anticancer activity of this plant, yet. MATERIALS AND METHODS: In the current study, cell viability, apoptosis induction, ROS production, mitochondrial apoptotic pathway, and ER stress mediators have been evaluated in breast cancer cells, MCF7, and MDA-MB-468 treated with D. maritima. RESULTS: Significant cytotoxic effects were observed in MCF-7 and MDA-MB-468 cells after exposure to D. maritima. Apoptosis induction was determined using Annexin-V-FITC and propidium iodide staining. Furthermore, an increase of ROS, loss of mitochondrial membrane potential, the release of cytochrome c, activation of caspases, and elevation in the Bax/Bcl-2 ratio was determined. D. maritima dose-dependently increased the mRNA expression of ER stress markers such as CHOP, ATF-4, GADD34, and TRIB3 in MCF-7, and MDA-MB-468 cells. CONCLUSION: These data suggest that D. maritima induces apoptosis in human breast cancer cells via the mitochondrial-mediated pathway. In addition, endoplasmic reticulum stress seems to be involved in D. maritima-induced cell death.
RESUMEN
BACKGROUND: One of the acquired biological hallmarks of tumor multistep development is the resistance of cancer cells to apoptosis; therefore, induction of apoptosis is an important therapeutic approach. Hypericum species are spread throughout the world and have been investigated for their biological properties. OBJECTIVES: Our previous studies had demonstrated cytotoxicity of Hypericum scabrum L. methanol extract against some tumor cell lines, suggesting the species for further studies. The objectives of the present study were to determine the most cytotoxic fraction of Hypericum scabrum L. and to assess the apoptosis induction ability of the most effective fraction as well as its methanol extract. The laboratory evidence has been presented to support the potency of Iranian Traditional Medicine (ITM) medicinal plants as a source of different biological activity surveys and drug discoveries. MATERIALS AND METHODS: The present research is a descriptive study. The sampling strategy was based on ITM data of cancer phytotherapy. Hypericum scabrum was collected from Alborz province, Iran (2012) and the herbarium specimen was taxonomically identified. The petroleum ether, dichloromethane, and methanol fractions have been evaluated for cytotoxicity against M-CF7, A-549, HT-29, and HepG-2 cell lines through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay. The apoptosis induction ability has been assessed by activated caspase-3 inspection and Annexin V FITC/PI (propidium iodide) assays. RESULTS: Di-chloromethane fraction demonstrated IC50 values of 25.72 µg/mL and 24.73 µg/mL against HT-29 and HepG-2 cell lines, respectively and IC50 values of petroleum ether fraction were 22.6 µg/mL and 18.31 µg/mL against HT-29 and HepG-2, respectively. The methanol fraction did not show cytotoxic activity. Both the methanol extract and the petroleum ether fraction of Hypericum scabrum L. revealed apoptosis induction ability. CONCLUSIONS: Considering the strong historical background about the therapeutic potential of the genus Hypericum and the considerable cytotoxic and apoptosis induction ability of Hypericum scabrum, this species is suggested for future biological studies.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: By studying the Iranian Traditional Medicine (ITM) Pharmacopoeia, we have collected information about medicinal plants which had been used to manage cancer-like disorders over eight hundred years, from medieval to the early modern era. Exploring the ITM herbal knowledge, the selected species have been subjected to MTT assay for examining their in vitro cyototoxic activity. MATERIALS AND METHODS: Cancer was reviewed through the ITM and some terminologies were acquired. Five ITM Pharmacopoeia in Arabic and Persian languages from 10th to 18th century AD were explored. These Pharmacopoeia contained the ITM plants which were used to cure cancer and cancer-like diseases. The ITM names were matched with the scientific names. Then the medicinal plants were collected, authenticated and were evaluated for cytotoxic activity using MTT assay, against MCF-7, HepG-2, A-549 and HT-29 cell lines. Finally, the apoptosis induction ability of the most cytotoxic medicinal plant was investigated by activated caspase 3 inspection in MCF-7 cell line. RESULTS: Six species of the evaluated medicinal plants revealed cytotoxic activity. The most cytotoxicity was observed in Tanacetum polycephalum subsp. argyrophyllum (K.Koch) Podlech with IC50 values of 28.3 µg mL(-1), 53.9 µg mL(-1) and 43.3 µg mL(-1) against MCF-7, A-549 and HT-29 cell lines, respectively. Caspase 3 activation was also observed in MCF-7 cells by Tanacetum polycephalum subsp. argyrophyllum. This is the first time that the cytotoxic activity of this species has been reported. CONCLUSION: In the present study, some reliable references of ITM have been introduced and though many technical difficulties, linguistic problems and some other hindrances were encountered during the study, using traditional medicine texts for medicinal plant selection could be considered as a helpful starting point in the field of cancer drug discovery.
