Alkaloidal Extract From <i>Carica papaya</i> Seeds Ameliorates CCl <sub>4</sub>-Induced Hepatocellular Carcinoma in Rats

Abstract

Background: Hepatocellular carcinoma (HCC) is the third cause of cancer-related mortality globally, however, available treatments are expensive and associated with adverse effects or poor treatment outcomes in advanced disease. Meanwhile, plants like Carica papaya have demonstrated hepatoprotective effects, and further studies may lead to the identification of newer and safer treatment options for HCC. Aim: To evaluate the anticancer activity of an alkaloidal extract derived from Carica papaya seeds using rodent models of hepatocellular carcinoma. Experimental Procedure: Carica papaya fruits were collected and authenticated. The seeds were isolated and air-dried. Alkaloidal extract was prepared from a 70% ethanol soxhlet crude extract and referred to as Carica papaya alkaloidal extract (CPAE). HCC was induced in 68 out of 84 healthy male Sprague Dawley rats by intraperitoneal injection of carbon tetrachloride (CCl4) for 16 weeks. These rats were put into five groups of 10; Carica papaya alkaloidal extract [(CPAE) (50, 100, and 200 mg/kg), Lenvatinib (4 mg/kg)], 1% dimethyl sulphoxide (DMSO), and 2 untreated groups (control and model). A prophylaxis study was performed with 10 rats by co-administration of CPAE (200 mg/kg) and CCl4 six hours apart for 16 weeks. Rats were sacrificed under anesthesia for histological, hematological, and biochemical analyses. Results and Conclusion: CPAE (100 and 200 mg/kg) significantly restored weight loss (48.44 and 51.75% respectively), reduced tumor multiplicity, and dose-dependently reversed liver histomorphological changes induced by CCl4 compared to the model group. CPAE (200 mg/kg) also significantly (p < 0.0001) reduced serum alpha-fetoprotein levels compared to the model group. Additionally, CPAE (100 and 200 mg/kg) significantly (p < 0.01) reduced bleeding time, improved prothrombin time, restored normal platelet count, and prevented the establishment of HCC in 16 weeks prophylactic study.