Study of anticancer effects of 3-methyladenine metabolite and curcumin loaded on histidine-functionalized cellulose carrier on HepG2 cancer cell line

Abstract

Introduction: Liver cancer is one of the deadliest cancers in the world today and it includes two types: primary and secondary. Primary cancer starts in liver tissue, while secondary cancer spreads to the liver from another organ. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and currently the most common cause of death in people with cirrhosis due to hepatitis B or C. The current treatments for this disease are surgery and chemotherapy, but these treatment methods have many side effects and reduce the survival rate. Therefore, scientists are looking for alternative treatments with the least side effects and the most effectiveness. The use of nanocarriers is a suitable option for these purposes. Cellulose is a natural polymer material that can be used in drug delivery purposes due to its many advantages, including biocompatibility, biodegradability and wide availability. The aim of this study is the synthesis of oxidized cellulose functionalized with L-histidine amino acid containing CUR and the effect of this nanocarrier containing drug along with 3-methyladenine metabolite on liver cancer cells in vitro. Methods: First, dialdehyde cellulose functionalized with L-histidine amino acid containing CUR (CUR/DAC-His) was synthesized and 3-methyladenine was added to them. Then, their physicochemical properties were determined and MTT, DAPI, apoptosis, cell cycle, western blot and real time PCR tests were performed to evaluate the effect on HepG2 cell line. Results: CUR/DAC-His showed a mean particle size of 218.3 nm with a zeta potential of about -8.34 mv and rod-like morphology. Also, the loading percentage of CUR was 95% and the percentage of CUR release was 66.59% with a sustainable and controllable release. The greater effect of 3-MA+CUR/DAC-His and then CUR/DAC-His than the free and combined state of drugs (3-MA-CUR) on the cell survival, cell apoptosis, autophagy and Bcl2 and Caspase3 expression were detected. In conclusion, cellulose nanocarrier functionalized with L-histidine increases the anticancer effect of CUR compared to its free state, and the addition of 3-MA enhances the lethal effect of the nanocarrier containing CUR. Keywords: Hepatocellular carcinoma, Cellulose nanocarrier, HepG2, 3-MA, CUR