Background: Despite recent breakthroughs in cancer treatment, non-small cell lung cancer (NSCLC) and breast cancer remain major causes of death from all malignancies. The epidermal growth factor receptor (EGFR) is an important mediator of the pathways involved in cell proliferation, apoptosis, and angiogenesis. Thus, its overexpression triggers several types of cancer, including NSCLC and breast cancer. Methods: In the current study, we synthesized new pyrimidine-tethered compounds (chalcone derivative (B-4), pyrazoline–carbothioamide (B-9), and pyrazoline–thiazole hybrids (BH1-7)). These compounds were then tested for cytotoxicity against A549 NSCLC and MCF-7 breast cancer cells. Results: Of these, B-4 displayed significant cytotoxicity against both cells (IC₅₀ = 6.70 ± 1.02 µM for MCF-7; IC₅₀ = 20.49 ± 2.7 µM for A549) compared to the standard agent lapatinib (IC₅₀ = 9.71 ± 1.12 µM for MCF-7; IC₅₀ = 18.21 ± 3.25 µM for A549). The anticancer potential of B-4 between Jurkat leukemic T cells and peripheral blood mononuclear cells (PBMCs) (healthy) was found to be selective. Mechanistically, 11.9% and 10.2% of A549 and MCF-7 cells treated with B-4, respectively, underwent apoptosis and B-4 produced 46% EGFR inhibition at a concentration of 10 μM. The B-4/EGFR complex obtained after induced fit docking was subjected to 300 ns of molecular dynamics simulation, which confirmed the stability of the complex in a mimicked biological environment. On the other hand, B-4 was shown to have drug-like properties by in silico pharmacokinetic estimation. Conclusions: B-4 is an EGFR inhibitor and apoptosis inducer for future NSCLC and breast cancer studies.

Propolis is a candidate for cancer treatment with its activity against different tumor cells and, has a wide spectrum of biological and pharmacological activities due to the diversity of its components. In this study, antitumorigenic activities of ethanol extract of propolis (EEP) and ethanol extract of propolis loaded niosome (PLN) were compared using 2D and 3D cell culture. Niosome formulations were prepared by thin film hydration technique. Cell viability of EEP and PLN was analyzed on MCF7, A549, MDA-MB-231, SK-MEL, SK-BR-3, DU145 and L-929 cell lines using MTT assay. L929, MCF7 and A549 cells were cultured using the 3D petri dish technique and their spherical forms were obtained after 142 h. After 24 h, PLN and EEP application, cell viability analysis was performed on 3D cultures with WST assay. As a result, niosome formulations containing EEP showed higher activity than ethanol extract of propolis in cancer cells. While a slow decrease was observed in cell viability in EEP treated cancer cells, it was observed that the percentage viability rates decreased in a shorter time in PLN treated cancer cells. Also, PLN can be used as an anticancer activity drug such as Doxorubicin, but this is not the case for EEP.

This research was carried out to determine the anti-tumorigenic, antioxidant and antimicrobial activities of extracts obtained from Juniperus oxycedrus L. oxycedrus (Cupressaceae) and Smilax aspera L. (Smilacaceae) fruits. The cytotoxic effects of ethanol extracts of Juniperus oxycedrus L. oxycedrus and Smilax aspera L. fruits were determined with six different tumorogenic cell lines including breast adenocarcinoma, small cell lung carcinoma, osteosarcoma, neuroblastoma and healthy kidney epithelial cells. Among the tested ethanol extracts of Juniperus oxycedrus L. oxycedrus and Smilax aspera L. fruits the ethanol extract obtained from Juniperus oxycedrus fruits was determined to have the highest anti-tumorigenic effect against small cell lung carcinoma with an IC50 value of 7.2 μg ml-1. At the end of cytotoxicity studies, ethanol extracts of Juniperus oxycedrus L. oxycedrus fruits proved to be good candidates for small cell lung carcinoma (A569). Antimicrobial effects were analyzed by the MIC test. MIC values of ethanol extracts of Juniperus oxycedrus L. oxycedrus and Smilax aspera L. fruits against Escherichia coli and Candida albicans were found to be 31.25 μg ml-1. Moreover, the radical scavenging capacity of Juniperus oxycedrus L. oxycedrus and Smilax aspera L. fruit extracts was elucidated. S. aspera L. (61%) and J. oxycedrus L. oxycedrus (47.3%) were found to have good free radical scavenging capacity.

Cancer remains the second leading cause of death worldwide, accounting for approximately 20% of annual mortalities. Lung, breast, colon, and melanoma are among the most common cancer types, especially in developing countries. Kojic acid and its synthetic derivatives are known for their wide range of biological activities and applications in medicine, cosmetics, food, and agriculture. Mannich base derivatives of kojic acid have been previously reported to exhibit promising cytotoxic potential on various tumor cell lines. In this study, a series of kojic acid–based Mannich bases containing a piperidine ring were synthesized and evaluated for their anticancer effects on several cancer cell lines (SK-MEL, MCF-7, MDA-MB-231, A549, HeLa, Hep3B, HT-29, Neuro2A) and one healthy cell line (Vero). Among the synthesized compounds, Compound 4, containing a piperidinopiperidine moiety, demonstrated the highest and broadest cytotoxic activity, with IC50 values of 1.62 ± 0.03, 1.87 ± 0.02, and 1.91 ± 0.04 µg/mL against MCF-7, Neuro2A, and SK-MEL cells, respectively. Flow cytometric analysis using the Annexin V method confirmed that Compound 4 induced apoptosis in a time- and concentration-dependent manner, leading to G1 phase arrest in MCF-7 cells.

Mannich bases synthesized from kojic acid have been determined in extensive studies conducted by our study group that they have a wide variety of biological activities. In this study, new anticancer-active compounds were synthesized from compounds with high anticancer activity. The compounds' structures were identified through the utilization of spectroscopic methods and elemental analyses. The cytotoxicity screening of the compounds were done by MTT assay on different human cancer cell lines. Compound 1 bearing iodomethyl moiety, showed remarkable cytotoxicity with IC50 values in the range of 8.11 and 21.24 µg/mL. The IC50 value on Vero (African green monkey kidney epithelial) is over 100 µg/mL which means low cytotoxicity against healthy cells. Compared to this, SK-MEL cells have 12 times less IC50 value, with a therapeutic index over 12. The closest cytotoxic effectivity to KOJI MG84 which is previously reported as a cytotoxic agent, is observed on the SK-MEL cell line in compound 1, with 4 times less cytotoxic activity.