Abstract
Background: Cervical cancer is one of the most prevalent malignancies in women in many countries worldwide. Therefore, the development and search for novel and effective anticancer agents have become very important issues. Datura seeds and leaves were used in the treatment of common cold, headache and asthma. However, its role in cancer growth has not been elucidated yet. The present study is aimed at investigating the cytotoxicity of the aqueous extract of the seeds of Datura inoxia against cervical cancer HeLa cells. Materials and Methods: The effect of aqueous extract of the seeds of Datura inoxia on cell death and intracellular targets that affect angiogenesis (VEGF), inflammation (IL-12, TNF- alpha ), apoptosis (caspase-3, -8 & -9) and antioxidant (superoxide dismutase & catalase) were determined by MTT assay, ELISA and enzymatic activity assay. In addition, Anti-VEGF neutralization effect was evaluated alone and in combination with aqueous extract, to assess whether it could result in augmented anticancer efficacy than the single agent. Results: Aqueous extract of the seeds of Datura inoxia inhibited growth of cancer cells in a dose and time-dependent manner. Experiments aiming to investigate the anti-angiogenic activity against HeLa, revealed that following the treatment, a dose-dependent decrease (p < 0.001) in the levels of VEGF secreted by the cells was recorded. In another set of experiments Aqueous extract potentiated (p < 0.001) the cell death induced by anti-VEGF antibody. VEGF and its receptors are established as major mediators of tumor cell growth and invasiveness; taken together; the results of these experiments suggest that datura possesses antiangiogenic activity. Although it appeared to decrease the levels of tumorigenesis factor, TNF- alpha (p < 0.05), it did not alter IL-12 level significantly. The pro-apoptotic effects were confirmed by significant (p < 0.001) increase in caspases-3 and -9 but not 8 activity. Significant increase in antioxidant enzymes (SOD, catalase) activity was also recorded. Conclusion: Aqueous extract of the seeds of Datura inoxia acts via multiple albeit specific molecular targets to elicit anti-carcinogenic activity thus might be a candidate for developing multifunctional anti-cancer agent through its inhibitory activity on several aspects of tumor growth and angiogenesis.