الفهرس 
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Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and the 3rd most common cancer-related death in the world. No effective therapeutic option exists for the treatment of the majority of patients with HCC. The available drugs exhibit severe side effects, poor therapeutic index, in addition to having high cost. This study was designed to examine different monocationic arylthiophene derivatives for possible use as chemotherapeutic agents against HCC either per se or as chemosensitizers. METHODS: The cell viability was determined after treatment with a dose of 50 µM concentration of each arylthiophene compound. Subsequently, the IC50’s for the most promising compounds were further determined using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The mechanisms of cytotoxicity for the tested compounds were further investigated using different methods. Moreover, the toxicity of the most active compound was investigated in male Swiss albino mice. RESULTS: Compound 2j proved to retain the highest cytotoxicity (IC50 = 2.9 ± 0.24 µM) in comparison to cisplatin (IC50 = 13.44 ± 1.7 µM) as a positive control. The selectivity index of compound 2j (SI = 3.67 ± 0.011) revealed the safety to normal lung fibroblast cells (WI-38) vs HepG2 cell line. Moreover, the most active compound 2j was not only able to inhibit cell migration in the wound-healing assay but to also inhibit cell division in the colony-formation assay. The anticancer effect of compound 2j on HepG2 cells was found to be partially via cell cycle arrest at G2/M phase, activation of the tumor suppressor p53 protein, and induction of apoptosis via both intrinsic and extrinsic pathways. Compound 2j has a potential sensitization activity and significantly reduced the IC50 values for the anticancer drugs doxorubicin, cisplatin, and taxol. In this study, the toxicity of compound 2j on liver, kidney, heart, spleen and lung of mice was studied and it was found that compound 2j has a dose-dependent toxic effect on all the tested organs. The slight changes caused by the dose 20 mg/kg in body weight indicate that the safe dose was the tenth of the LD50 dose (i.e.10 mg/kg). CONCLUSION: The tested arylthiophenes showed a potent cytotoxicity against HepG2 cells and were safe to normal cells. The most active compound 2j was found to be able to inhibit cell division and cell migration and also to induce apoptosis via intrinsic and extrinsic pathways and that was evidenced by elevating caspases-8, -9 and -3. Compound 2j also has a sensitization effect on the standard anticancer drugs investigated.