ABSTRACT
Objective: To find new compounds in order to overcome the mainstay of metastatic breast cancer due to the adverse side effects from, and increasing resistance to, current chemotherapeutic agents. Methods: α-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma (BT474) cell line and non-tumorigenic epithelial tissue from mammary gland (MCF-10A) were used. Cell viability assessment was calculated by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cell morphology was investigated by light microscopy. By flow cytometry analysis, programmed cell death was observed using annexin Ⅴ and propidium iodide staining while cell-cycle arrest was observed using propidium iodide staining. Change in transcriptional expression was evaluated by real-time quantitative reverse transcription PCR. Results: In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the result revealed α-mangostin and apigenin were more cytotoxic to BT474 cells. Longer exposure times to α-mangostin and apigenin caused more floating cells and a lower density of adhered cells with more vacuoles present in the colonies in BT474 only. α-Mangostin and apigenin caused necrosis in BT474 cells in a 24 h exposure, but a small amount of early apoptotic cells could also be detected at 24, 48 and 72 h exposure, whereas doxorubicin caused early apoptosis to BT474 cells at 24 h. Transcript expression and activity analysis supported caspase-3 was involved in the death of BT474 cells treated by all compounds. Moreover, α-mangostin and apigenin arrested the cell-cycle at the G1-phase, but at the G2/M-phase by doxorubicin. All three compounds induced a change in transcript expression levels of inflammation-associated, proto-oncogene, autophagy-associated and apoptosis-associated genes. Conclusions: α-Mangostin and apigenin are worth investigating as potential new sources of chemotherapeutic agents for breast cancer treatment.
ABSTRACT
Aims: Honey and propolis have long been used in traditional medicine whilst honey is consumed as food. A screening for various bioactivities in honey from Apis florea and A. andreniformis, and the crude water and ethanol extracts of propolis from A. mellifera and Tetragonula laeviceps, from Thailand are reported. Study Design: Cell based study. Place and Duration of Study: Department of Biology, Faculty of Science, Chulalongkorn University, between June 2010 and April 2011. Methodology: Various components such as protein, sugar, gluconic acid were assayed in honey while total sugar, reducing sugar, total polyphenol and flavonoid content were assayed in crude propolis. Samples were tested for in vitro antimicrobial, in vitro antiplasmodial and antiproliferative activities. Results: The crude propolis extracts showed good bioactivities. Antibacterial activity was found against Bacillus cereus (a model Gram-positive bacteria) in the water extracts of propolis from T. laeviceps (TLW) and A. mellifera (AMW), with MIC values of 50 and 100 μg/ml, respectively, whilst against Escherichia coli (a model Gram-negative bacteria), TLE revealed some 24.0% growth inhibition. Most interestingly, the ethanol extract of propolis from T. laeviceps (TLE) displayed a strong anti-malarial activity with a MIC of 4.48 μg/ml against in vitro Plasmodium falciparum growth, whilst AMW revealed a high inhibition of Mycobacterium tuberculosis growth (74.3%). Furthermore, TLW (50 μg/ml) provided the highest anti-Herpes Simplex Virus type 1 replication activity at 33.0% without any sign of cytotoxicity to the host Vero cells. Finally, in vitro anti-proliferation activity against four cancer cell lines in tissue culture was noted with IC50 vales ranging between 25.5 - 29.3 and 26.8 – 49.5 μg/ml for TLE and AME, respectively. Conclusion: Overall, the propolis of Thai A. mellifera and T. laeviceps exhibit diverse and some novel bioactivities worthy of further enrichment and characterization.