ABSTRACT
Sulforaphane (SFN) may hinder carcinogenesis by altering epigenetic events in the cells; however, its molecular mechanisms are unclear. The present study investigates the role of SFN in modifying epigenetic events in human cervical cancer cells, HeLa. HeLa cells were treated with SFN (2.5 µM) for a period of 0, 24, 48, and 72 hours for all experiments. After treatment, expressions of DNMT3B, HDAC1, RARß, CDH1, DAPK1, and GSTP1 were studied using RT-PCR while promoter DNA methylation of tumor suppressor genes (TSGs) was studied using MS-PCR. Inhibition assays of DNA methyl transferases (DNMTs) and histone deacetylases (HDACs) were performed at varying time points. Molecular modeling and docking studies were performed to explore the possible interaction of SFN with HDAC1 and DNMT3B. Time-dependent exposure to SFN decreases the expression of DNMT3B and HDAC1 and significantly reduces the enzymatic activity of DNMTs and HDACs. Molecular modeling data suggests that SFN may interact directly with DNMT3B and HDAC1 which may explain the inhibitory action of SFN. Interestingly, time-dependent reactivation of the studied TSGs via reversal of methylation in SFN treated cells correlates well with its impact on the epigenetic alterations accumulated during cancer development. Thus, SFN may have significant implications for epigenetic based therapy.
ABSTRACT
Herbs are extensively consumed in the United Arab Emirates for their flavoring and medicinal properties. This study aimed at determining the concentration of heavy metals in selected traditional herbs consumed in the United Arab Emirates (UAE). A total of 81 samples of seven herbs, parsley (Petroselinum crispum), basil (Ocimum basilicum), sage (Salvia officinalis), oregano (Origanum vulgare), mint (Mentha spicata), thyme (Thymus vulgaris), and chamomile (Matricaria chamomilla), were purchased from the local market in Dubai and analyzed for their cadmium, lead, copper, iron, and zinc contents. Microwave-assisted digestion was applied for the dissolution of the samples and heavy metals concentration was determined using Atomic Absorption Spectrometry (AAS). Metals were found to be present in varied concentrations in the herb samples. The concentration ranges were found as follows: less than 0.1-1.11 mg·kg(-1) for cadmium, less than 1.0-23.52 mg·kg(-1) for lead, 1.44-156.24 mg·kg(-1) for copper, 12.65-146.67 mg·kg(-1) for zinc, and 81.25-1101.22 mg·kg(-1) for iron. The findings of the study suggest that most of the analyzed herbs contained unsafe levels of heavy metals that exceeded the World Health Organization (WHO) permissible limits (PL).
