Effect of 2z-(1,2-dihydro-6-methoxy-2-oxo-1-pentyl-3h-indol-3-ylidene) hydrazide benzoic acid (MDA77) on KLK-6 and KLK-8 protein levels in cervical cancer cell line

Effect of 2Z-(1,2-Dihydro-6-Methoxy-2-Oxo-1-Pentyl-3H-Indol-3-ylidene) Hydrazide Benzoic Acid (MDA77) on KLK-6 and KLK-8 Protein Levels in Cervical Cancer Cell Line Cervical cancer is the fourth most common cancer type in women worldwide, especially caused by Human Papillomavirus (HPV), after breast, colorectal and lung cancer. It increases mortality by causing resistance to treatment. Despite advances in early diagnosis and effective treatment strategies, cervical cancer continues to be a major health problem on a global scale. Despite advances in conventional and targeted therapies, inadequate primary treatment response and treatment-related toxicity are among the main obstacles encountered in the management of cervical cancer. The kallikrein-related peptidase (KLK) gene family is encoded by the largest protease gene cluster in the human genome and consists of 15 highly conserved serine proteases. Kallikrein (kininogen) is an enzyme that cleaves proteins between the amino acids arginine and lysine. KLKs play an important role in the regulation of inflammatory response, thrombosis and blood coagulation. Kallikrein 6 (KLK-6) is a trypsin-like serine protease. KLK-6 has been found to play a role in the remodeling of the extracellular matrix, tumor invasion, and the regulation of cancer signaling pathways such as PI3K, as well as providing nervous system plasticity. KLK-8 is an extracellular serine protease that plays a role in biological activities such as epidermal proliferation, differentiation, and nervous system plasticity regulation. Overexpression of KLK-8 has been observed in many malignancies, including ovarian, cervical, and lung cancers. Cannabinoids are active compounds obtained from the plant species Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Cannabinoids show their effects through endocannabidinoid system receptors (CB1, CB2, and G-protein coupled receptors). Studies have shown that cannabinoids inhibit tumor growth. Cannabinoids have been reported to have anti-tumorigenic activity, such as inhibiting tumor cell proliferation and directing apoptosis. In this study, the effects of cannabinoid derivative MDA77 and epigenetic regulator A-485 as a control drug on KLK-6 and KLK-8 protein levels were investigated by ELISA method using HeLa cell line. The findings show that MDA77 has a stronger inhibitory effect on KLK-6 and KLK-8 proteins than A-485. It is thought that MDA77 may be a potential therapeutic agent candidate in cervical cancer. Keywords: A-485, Cancer, Cervical cancer, KLK-6, KLK-8, MDA77