Chloroquine diphosphate suppresses liver cancer via inducing apoptosis in Wistar rats using interventional therapy

Abstract

Liver cancer ranks as the second leading cause of cancer-associated mortality worldwide. To date, neither current ablation therapy nor chemotherapy are considered ideal in improving the outcome of liver cancer. Therefore, more effective therapies for treating this devastating disease are urgently required. Interventional therapy has been used for numerous years in the treatment of different types of cancer, and is characterized by the direct delivery of anticancer drugs into the tumor. It has been reported that antimalarial chloroquine diphosphate (CQ) exerts effective anticancer activity against several types of cancer. However, its effect on liver cancer remains unclear. Therefore, in the present study, 2D monolayer cell culture and 3D spheroid in vitro models, and a rat model, were utilized to investigate the effect of CQ on liver cancer. CQ demonstrated an effective anticancer effect on HepG2 cells and 3D liver spheroids. Furthermore, the drug significantly inhibited cell growth and viability in the 2D and 3D in vitro models. The CQ-based intervention treatment effectively attenuated tumor size and weight, increased food intake and consumption of drinking water, and improved body weight and survival rate of rats in the in vivo model. In addition, treatment with CQ potently increased the expression levels of the apoptosis-related genes. Taken together, the findings of the present study may provide a novel insight into the development of safe and effective treatments for liver cancer.

Combination of chloroquine diphosphate and salidroside induces human liver cell apoptosis via regulation of mitochondrial dysfunction and autophagy

“…These reports indicated that autophagy may also be a therapeutic approach for cancer and that inhibition of autophagy significantly promotes occurrence of apoptosis in the development of cancer. Moreover, reports indicate that cQ and interventional therapy combination may exert a synergistic effect and induce apoptosis in Wistar liver cancer rats (46,47). Similar to these results, in the present study, Sal induced apoptosis and autophagy in the human 97H liver cancer cell line.…”

Autophagy Inhibitor Chloroquine Downmodulates Hepatic Stellate Cell Activation and Liver Damage in Bile-Duct-Ligated Mice

“…For instance, autophagy inhibition by chloroquine (CQ) reduced liver damage in the ischemia/reperfusion model of acute phage but worsened when treatment was prolonged [ 5 ]. CQ treatment was found to have positive effects in chronic [ 6 ] and acute [ 7 , 8 ] CCl 4 models of liver failure; in addition, it prevented autoimmune hepatitis in humans [ 9 ] and inhibited liver cancer [ 10 , 11 ]. Additionally, the use of an autophagy inducer such as rapamycin mitigated liver damage in a model of nonalcoholic fatty liver disease [ 12 ] as well as in liver diseases of different etiologies [ 13 ].…”