Abstract
A current hurdle in cancer management is the intrinsic or acquired resistance of cancer cells to chemical agents that restricts the efficacy of therapeutic strategies. Accordingly, there is an increasing desire to discover new natural compounds with selective toxicity to combat malignancies. In present study, the cytotoxic and apoptosis- inducing activities of ferutinin, a terpenoid derivative from Ferula ovina, were investigated on human breast (MCF7) and bladder (TCC) cancer cells as well as normal fibroblasts (HFF3).The toxicity and DNA damage inducing effects of ferutinin were studied by MTT and comet assays, DAPI and PI staining and DNA laddering. The IC50 values of ferutinin were identified and compared with routine prescribed drugs, doxorubicin and vincristine, by MTT test. Alkaline comet assay and DAPI staining revealed DNA damage due to ferutinin, which was significantly (p<0.001) higher in MCF7 and TCC than HFF3 cells. Apoptosis induction was evidenced by PI staining and DNA laddering. Our results suggest that ferutinin could be considered as an effective anticancer agent for future in vivo and clinical experiments.
Highlights
Cancer is the second leading cause of death in the world
The cytotoxic and apoptosisinducing activities of ferutinin, a terpenoid derivative from Ferula ovina, were investigated on human breast (MCF7) and bladder (TCC) cancer cells as well as normal fibroblasts (HFF3).The toxicity and DNA damage inducing effects of ferutinin were studied by MTT and comet assays, DAPI and propodium iodide (PI) staining and DNA laddering
Our results suggest that ferutinin could be considered as an effective anticancer agent for future in vivo and clinical experiments
Summary
Cancer is the second leading cause of death in the world. In 2005, the global incidence of cancer was 11 million and it is expected to increase to an incidence of 15.5 million by 2030 (Strong et al, 2008). A lot of progress has been achieved in cancer therapy and management, the existence of resistant cancer cells has restricted the efficiency of current radio and chemotherapy regimens (Rivera and Gomez, 2010). This drawback points to the need of expanding the exploration for novel, more effective and preferably natural compounds with anticancer properties. Genus Ferula (Apiaceae) contains more than 130 species, among which 30 species have been represented in Iranian flora (Mozaffarian, 1996). Ferula species are good sources of biologically active compounds such as terpenoid coumarins and sesquiterpene derivatives (Iranshahi et al, 2007; Iranshahi et al, 2009) and our previous studies demonstrated that these derivatives could reverse the drug resistance of cancerous cells (Rassouli et al, 2009; Mollazadeh et al, 2010; Rassouli et al, 2011a), and show cytotoxic (Rassouli et al, 2011b), antileishmanial (Iranshahi et al, 2007), and cancer chemopreventive (Iranshahi et al, 2008; Iranshahi et al, 2010) activities
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