Investigating the molecular mechanisms of the effects of dwarf nettle (Urtica urens) on prostate cancer


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Pamukkale Üniversitesi, Fen-Edebiyat Fakültesi, Biyoloji Bölümü, Türkiye

Tezin Onay Tarihi: 2014

Tezin Dili: Türkçe

Öğrenci: Gülsüm Terzioğlu

Danışman: Alaattin Şen

Özet:

Despite recent advances in early diagnosis and treatment, cancer is still the first leading cause of death during the last 20 years. In addition to conventional treatments such as chemotherapy and radiation therapy alternative and complementary therapies are also frequently used among the cancer patients not only in Turkey but also all over the world. As a result, the popularity of herbal preparations as alternative and complementary therapies has been ever growing and they constitute great importance in terms of public health as well as economic value. The scope of this proposed research project is to determine the unknown phytochemical constituents of a widely used traditional therapeutic medicinal plant i.e. Urtica urens (small nettle) and is to investigate it's anticarcinogenic, and tumor suppressor effects at the molecular level. For this purpose, hexane and ethly acetate extracts was prepared from the leaves of Urtica urens using different solvents. Analyses of these extract by GC/MS and LC/MS was showed that hexane extract is rich with unsaturated fatty acids and ethyl acetate extract is enriched with the phenolic compounds. The cytotoxic effect of extracts obtained from Urtica urens was determined in LNCaP cells by this study and the results was showed that the LD50 values of the hexane and ethyl acetate were found 42,77 µg/ml and 33,96 µg/ml respectively. This result was demonstrated that both extracts may have high cytotoxic and anti-carcinogenic activity. After that, changes that in mRNA and protein levels of 31 genes related with different cellular pathways was investigated and it was identified that ethyl acetate extracts induced apoptosis and tumor suppressor genes because of its phenolic compounds. Moreover, it was detected significant changes in 34 different cellular pathway as a result of whole genome transcriptome analysis of ethyl acetate extracts treated cells. Besides all, it was detected that hexane extracts inhibited activity of topoisomerase I and II enzymes. Moreover, the mRNA levels of nuclear receptors that are responsible for the drug transcriptional regulation of drug metabolizing enzymes was increased significantly by ethyl acetate treatment. All of these results reveled that this herb showed anticarcinogenic and cytotoxic activity by changing different cellular pathways. Morever, it was determined that this herb may cause changes in the metabolism of other drugs was determined by this study. This study supplied new clues for other pharmacological and toxicological studies of urtica species.