الفهرس 
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Abstract
Introduction: Global cancer statistics showed that ovarian cancer was the second most prevalent gynecological cancer in 2020 whilst, lung cancer remained the most aggressive type of cancer accounting for an estimated 1.8 million fatalities. Despite substantial evolutions in therapeutic options, cancer is frequently fatal. Cancer cells are generated every day due to the cumulative acquisition of genetic abnormalities in an organism ranging from around 2000 to over 3000, which are normally destroyed by immune cells. Some of these cells, however, avoid immune surveillance, resulting in their survival and unregulated proliferation. Radiation and anticancer medications may be effective against newly formed cancer cells, but these cells eventually become resistant to these treatments.
Targeting the apoptotic pathway is a spectacular strategy to discovering new anticancer medicines as it is indiscriminative to cancer type. Cancer is characterized by many mutations in intrinsic and extrinsic pathways that enable cells to avoid apoptosis. A more effective cancer treatment would be made possible by the capacity to target and activate an apoptotic pathway.
Methods: Two different cancer cell lines (OVCAR-3 and A-549 cell lines) were utilized in this work. MTT assay was used to assess CMB’s cytotoxicity towards OVCAR-3 and A-549 cell lines. Cell apoptosis was confirmed using annexin V/PI staining technique. The cell cycle distribution was assessed using a flow cytometer. qRT PCR was used to assess the expression of P53, P21, BAX, and BCL2. Caspase-3 and MAPK (ERK1/2, MKK4, MKK7 and JNK1/2) protein expressions were investigated by western blot assay.
Findings: MTT assay of CMB towards OVCAR-3 and A-549 showed remarkable cytotoxicity impact. CMB cytotoxicity was directed toward OVCAR-3 cells over A-549 cells. Annexin V/PI staining assay elucidated that CMB induced intrinsic apoptosis of OVCAR-3 and A-549 cells which confirmed by increased BAX/BCL2 ratio. Cell cycle assay showed that CMB induced S phase cell cycle arrest in both cell lines. In addition, our results showed that CMB treatment upregulated P53, P21 and BAX expression in a time dependent approach, whilst BCL2 gene expression was drastically downregulated following CMB treatment. Furthermore, CMB downregulated p-ERK1/2, p-MKK4, p-MkK7 and p-JNK1/2 in a time dependent fashion, whilst the expression of cleaved caspase-3 was remarkably increased after CMB treatment in a time dependent way which is a characteristic of apoptosis.
Conclusions: The present study illustrated that CMB displayed marked cytotoxicity against ovarian and lung cancer cells. Mechanistically, CMB showed anti-proliferative activity towards ovarian and lung adenocarcinoma cells through inducing apoptosis via a mitochondrial apoptotic pathway mediated by P53/BAX/Bcl-2 and caspase-3 along with arresting the cell cycle at S phase via modulating the MAPK signaling pathway. Accordingly, CMB could be considered as a promising anticancer agent for both ovarian cancer and lung adenocarcinoma. However, further in vivo work is recommended to confirm our findings and fully discover the underlying mechanisms of CMB-mediated signaling pathways.