We investigated the cytotoxic and apoptotic effects of a methanol extract of Centaurea nerimaniae, a plant endemic in Turkey, on HeLa and MDA-MB-231 cells. Eight concentrations of C. nerimaniae extract were applied to cells, and cytotoxic effects were measured using the xCELLigence system. The TUNEL assay was used to assess apoptotic cell death and immunohistochemistry was used to determine active caspase-3 using the effective cytotoxic doses of the extract. Doses of 1.42 mg/ml C. nerimaniae inhibited the growth of HeLa cells and 3.67 mg/ml C. nerimaniae inhibited the growth of MDA-MB-231 cells in a dose- and time-dependent manner. The apoptotic indexes for HeLa and MDA-MB-231 cells were increased significantly compared to control groups. Immunohistochemistry showed that the number of caspase-3 immunostained cells increased in the extract treatment groups for both HeLa and MDA-MB-231 cells. In the MDA-MB-231 cell line, caspase-3 immunostaining was observed in nuclei and/or cytoplasm in the extract treated group. Caspase-3 activation was greater in HeLa cells than in MDA-MB-231 cells. We found that the extract of C. nerimaniae had a strong antiproliferative effect and induced apoptosis via caspase-3; MDA-MB-231 cancer cells were more resistant than HeLa cells.

We suggested that this endemic plant extract seems to be a new promising therapeutic approach in cancer.

Background/Aim: We aimed to investigate the synergistic effects of apigenin and curcumin on the cross-talk between apoptosis and autophagic cell death, as well as on paraptosis in HeLa cells. Materials and Methods: Cell viability was measured using the MTT assay. Synergistic effects were measured using the Bliss independence model. qRT-PCR was used to study the expression of genes related to apoptosis, autophagic cell death, and cross-talk. GRP78/BiP immunostaining was used to identify endoplasmic reticulum (ER) stress. Results: Treatment with a combination of apigenin and curcumin increased the expression levels of genes related to cell death in HeLa cells 1.29-to 27.6-fold. The combination of curcumin and apigenin showed a synergistic anti-tumor effect via cross-talk between processes leading to apoptosis and autophagic cell death, as well as ER stress-associated paraptosis. GRP78 expression was down-regulated, and massive cytoplasmic vacuolization was observed in HeLa cells. Conclusion: The combination of curcumin and apigenin is an effective potential therapeutic for cervical cancers.Cancer is a disease caused by the abnormal proliferation and differentiation of cells and is governed by tumorigenic factors (1). Cervical cancer is a major cause of death among young women. There have been significant advances in the diagnosis and treatment of cervical cancer (2). One of the most effective ways of treating cancer is chemotherapy.

: Cervical cancer is one of the frequent types of cancer seen in females. It has been suggested that natural compounds can be used effectively for cancer treatment. Apoptosis and autophagy related cell death play important roles in suppression of tumorigenesis. Apigenin and curcumin are natural products isolated from plant extracts known to have antitumoral, antibacterial and antiviral effects. Varying doses of curcumin and apigenin were applied to HeLa cancer cell lines. The expression of the genes related to apoptosis and/or autophagy related cell death were measured using qRT-PCR and cell viability was measured using MTT assay. Our results showed that curcumin and apigenin are effective on apoptosis and autophagy related cell death in HeLa cells. We suggested that these natural products seem to be a new promising therapeutic approach in cancer.

Hipofiz bezinin ön bölümü (adenohipofiz) vücudumuzdaki diğer iç salgı bezlerinin çalışmasını kontrol eden, 5-7 mm büyüklüğünde bir salgı bezidir. Adenohipofiz, çeşitli trofik hormonları salgılamak üzere farklılaşmış hücreler içerir. Bu hücrelerin çeşitli genetik, epigenetik ve çevresel faktörlerle etkileşimi sonucunda çoğunluğu iyi huylu olan hipofiz tümörleri (hipofiz adenomları) ortaya çıkabilir. Hipofiz adenomları arasında tanı ve tedavisi en zor olarak bilinen ACTH-salgılayan adenomlar böbreküstü bezini aşırı uyararak kontrolsüz miktarda kortizol salgılanmasına neden olur. Vücutta yol açtığı değişikliklere Cushing hastalığı adı verilir. Cushing hastalığının USP8, USP48, EGFR, p16, p21 gibi birçok farklı genin işlevinin kaybolmasına bağlı olarak ortaya çıktığı bilinmektedir. Bunun dışında ilgili genlerin metillenmesi ve asetillenmesi gibi çeşitli epigenetik modifikasyonlar ve miRNA’lar gibi çeşitli düzenleyicilere maruz kalması sonucunda da Cushing hastalığı görülmektedir. Bu genlerin ve proteinlerin işlevlerinin belirlenmesi sayesinde yeni tedavi stratejilerinin geliştirilmesi mümkün olacaktır.