The aim of this study is to investigate the potential inhibitory effect of α-chaconine and α-solanine on RL95-2 estrogen receptor (ER) positive human endometrial cancer cell line and to identify the effect of these glycoalkaloids on the Akt signaling and ERα. The cell proliferation profiles and the cytotoxicity studies were performed by Real-Time Cell Analyzer (xCELLigence) and compared with Sulphorhodamine B (SRB) assay. The effects of α-chaconine (2.5, 5, 10 µM), α-solanine (20, 30, 50 µM), API-1 (25 µM) and MPP (20 µM) effects on Akt (Ser473) and ERα (Ser167) expressions evaluated by Western blot and qPCR method. Their IC₅₀ values were as α-chaconine (4.72 µM) < MPP (20.01 µM) < α-solanine (26.27 µM) < API-1 (56.67 µM). 10 μM α-chaconine and 20, 30 and 50 μM α-solanine were effective in decreasing p-Akt(Ser473)/Akt ratio compared to positive control API-1. When the p-ERα/ERα ratios were evaluated, it was observed that α-chaconine (2.5, 5, 10 μM) and α-solanine (50 μM) were as effective as the specific ERα inhibitor MPP in reducing the ratio of p-ERα/ERα compared to the control group. In conclusion, it has been shown that the proliferation of α-chaconine and α-solanine in human endometrial carcinoma cells reduces the expression and activity of the Akt and ERα signaling pathway.

Background: Endometrial cancer is one of the most common types of cancer. For this reason, various studies have been carried out on its treatment and the effects of natural products on this disease. Objectives: This study aimed to examine the growth inhibitory effects of Eryngium kotschyi Boiss. ethyl acetate [EKE] and butanol [EKB] obtained from the main methanol [EKM] extract from the aerial parts on human endometrium carcinoma [RL95-2] cells and their synergistic effect with cisplatin or doxorubicin. Methods: RL95-2 cells were treated with E. kotschyi extracts either alone or in combination with cisplatin or doxorubicin. The effects on cell growth were determined using the MTT assay and real-time cell analysis xCELLigence. Results: The extracts demonstrated growth inhibitory activity, with a certain degree of selectivity against the RL95-2 cell line. Synergistic effects of EKE/cisplatin or doxorubicin at different concentration levels were demonstrated in RL95-2 cells. In some instances, the EKE/doxorubicin combinations resulted in antagonistic effects. The reduction level of cell viability was different and specific to each combination for the RL95-2 cell line. Conclusion: The growth inhibitory activity of cisplatin or doxorubicin, as a single agent, may be modified by combinations of the extracts and be synergistically enhanced in some cases. A significant synergistic effect of EKE on the RL95-2 cell line with cisplatin and doxorubicin was observed. This cytotoxic effect can be investigated in terms of molecular mechanisms. This study is the first of its kind in the literature. The mechanisms involved in this interaction between chemotherapeutic drugs and plant extracts remain unclear and should be further evaluated.

The Centaurea species (Asteraceae) is widely used in folk medicine. However, its apoptotic effects have not been adequately determined. Centaurea lycaonica is an endemic species belonging to the Centaurea L. genus. In this study, methanol (CHM) and dichloromethane (CHD) extracts obtained from the aerial part of C. lycaonica were treated to human cervical carcinoma (HeLa) cells to investigate their cytotoxic effects using Sulforhodamine B (SRB) assay and xCELLigence Real‐Time Cell analyzing system, in addition to their apoptotic effects by measuring caspases. As a result, the IC ₅₀ value of CHD and CHM on HeLa cells was calculated respectively as 39.27 μg/mL and 516.50 μg/mL. Increased activity of caspase‐3 and ‐9, along with a higher Bax/Bcl‐2 ratio, was observed in the HeLa cells at 30 and 100 μg/mL concentrations for CHD and 240 μg/mL for CHM. Significant cytotoxic effects through the mitochondrial apoptotic pathway were shown for the HeLa cells. LC‐HRMS determined the phytochemical content of extracts. The major compounds, diosmetin, and apigenin, were detected in the CHD extract, and chlorogenic and quinic acid were detected in the CHM extract. Apoptosis is induced primarily by CHD, which contains a high amount of diosmetin and is a promising candidate for anticancer research.

Centaurea L. cinsine ait birçok tür, dünyanın çeşitli bölgelerinde endemik olarak varlığını sürdürmekte ve halk hekimliğinde kullanımlarıyla literatürde yerini almaktadır. Söz konusu cinse ait bazı türlerin servikal kanser hücre hattı üzerindeki sitotoksisitesi incelenmiştir. Bu çalışmada Türkiye’ye endemik ve hakkında yok denecek kadar az sayıda çalışma bulunan Centaurea lycaonica türünün kök kısmından hareketle, 24 saat maserasyon yöntemiyle hazırlanmış diklorometan (CRD) ve metanol (CRM) ekstrelerinin 48 saatlik maruziyette insan servikal kanser hücre hattındaki (HeLa) sitotoksik etkisinin araştırılması amaçlandı. Bitki ekstresinden hazırlanan farklı konsantrasyonların hücre canlılığına etkisi çalışma prensipleri farklı olan MTT ve xCELLigence GZHA sistemi kullanılarak araştırıldı ve IC50 değerleri belirlendi. Sonuç olarak, CRD ve CRM ekstrelerinin MTT bulguları, xCELLigence analiziyle tutarlı olup HeLa hücrelerinde sitotoksik etkiye sahip olduğu bulundu. C. lycaonica türünün kanser tedavisinde yeni bir doğal kaynak olarak değerlendirilebileceği düşünüldü. Bu çalışmanın, Türkiye’ye endemik birçok türün biyolojik aktivite ve etki mekanizmalarının aydınlatılmasını teşvik edeceği düşünülmektedir.