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AbstractThe IL6/JAK2/STAT3 axis dysregulation and the related downstream pathways are a major contributor to the progression of non-small-cell lung carcinoma (NSCLC) and mainly affect apoptosis. Furthermore, tubulin inhibitors are potential chemotherapeutic agents against NSCLC. In this study, we have provided new molecular insights into the antiproliferative activity of six 3β-acetoxy-5α-androstane heterocycle compounds against NSCLC. The cell line A549, which represents a good model of NSCLC, was used to evaluate the antitumour activity of tested androstane derivatives, and non-cancerous gingival mesenchymal stem cell line (GMSC) were used to assess the specificity and toxicity of the tested compounds. Further on, molecular docking predictions were used to determine the molecular targets for the most promising cytotoxic compound. To assess apoptosis and cell cycle progression in treated A549 cells, flow cytometry was used. RT-qPCR and ELISA analyses were used to gain deep insights into cellular and molecular mechanisms. Results revealed that compound 4has potential cytotoxicity on A549 cells, with lower IC50value (27.36 μM). Moreover, in silico, compound 4showed a good binding affinity to JAK2 and tubulin-colchicine soblidotin molecular targets. This was further confirmed on the molecular level. Compound 4has also led to apoptosis and increased fragmentation of DNA, and mitochondrial dysfunction. Our findings have provided good evidence that compound 4may be a dual inhibitor of IL6/JAK2/STAT3 and tubulin formation in lung cancer. These findings support further molecular exploration of this androstane derivative as promising anti-lung cancer agent.Communicated by Ramaswamy H. Sarma

Background: Breast cancer is the common cause of deaths among women globally with 15% mortality globally. Introduction: Today, about 80% of the rural population depends on natural products as primary health care. Pulicaria crispa (L., family Compositae) is utilized in traditional medicine for curing colds, coughs, colic, and excessive sweating and as a carminative. Methods: The extracts of Pulicaria crispa; grown in Saudi Arabia; were assessed to measure the cytotoxicity with MDA-MB-231 breast cancer cell lines. Soxhlet extraction was utilized for stem, leaves and flower with 70% ethanol. The cytotoxicity of the extracts with MDA-MB-231 breast cancer cells was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Results: The apoptotic cellular morphological alterations were detected by fluorescence microscopes. The results indicated that Pulicaria crispa exhibited a strong anticancer activity with a halfmaximal inhibitory concentration (IC50) of 180 μg/mL against breast cancer cells. The loss in cell integrity, shrinkage of cytoplasm, and cell detachment were seen in the extract treated with MDAMB- 231 cells. The cell death was due to membrane destruction. Conclusion: Pulicaria crispa extracts indicated significant cytotoxicity against human breast cancer cells (MDA-MB-231 cells). The extract of this plant may be given to the patients having breast cancer.