Suppression of tumor growth and apoptosis induction by pomegranate seed nano-emulsion in mice bearing solid Ehrlich carcinoma cells

Abstract

Despite the high antioxidant and penetration ability of pomegranate seed oil (PSO), the in vivo antitumor activity of PSO nano-emulsion has not been well investigated. Therefore, this study was undertaken to estimate the antitumor activity and safety of PSO nano-emulsion in mice bearing Ehrlich solid carcinoma cells. For tumor inoculation, about 2 × 106 viable Ehrlich tumor cells (200 µl) were implanted intramuscularly in the left thigh of hind leg. Once a solid tumor appears on the 10th day of transplantation; the mice were randomly divided into five groups (5 animals/group). Characterization of the PSO nano-emulsion using a Zeta sizer Malvern instrument and transmission electron microscope (TEM) revealed that the PSO nano-droplets were well dispersed with an average particle size of 8.95 nm and a spherical shape. Treatment with PSO nano-emulsions caused a significant reduction in the tumor size and weight, in a dose dependent manner, compared to tumor control group. Marked dose dependent elevations in the DNA damage level together with significant increases in the tumor suppressor p53, Bax and Caspase genes and reductions in the anti-apoptotic Bcl2 gene were also observed in the tumor tissue of mice given PSO nano-emulsions. Histological examination also revealed apoptosis and necrosis of tumor cells and tumor infiltration with inflammatory cells after PSO nano-emulsion treatment. However, high DNA damage was noticed in the liver and kidney tissues of mice given the highest dose of PSO nano-emulsion (400 mg/kg). Therefore, we concluded that PSO nano-emulsion exhibited a potent antitumor activity through induction of DNA breaks that triggers apoptosis of tumor cells but the highest dose caused genotoxicity to liver and kidney tissues, thus it is recommended to use doses lower than 400 mg/kg of PSO nano-emulsion as an alternative drugs for chemotherapy.

Pomegranate seeds: a comprehensive review of traditional uses, chemical composition, and pharmacological properties

“…Advanced drug delivery systems such as micelles, liposomes, nanoparticles, and nanoemulsions offer promising avenues for improvement. PSO nanoemulsions have demonstrated potent anti-tumor activity by inducing apoptosis in tumor cells through DNA breaks, suggesting their potential as an alternative to chemotherapy ( Mohamed et al, 2023 ). Sahafi et al (2021) utilized ultrasonic emulsification to create PSO nanoemulsions loaded with alpha-tocopherol, revealing their favorable properties even in harsh environmental conditions.…”

Trichinella spiralis Larval Extract as a Biological Anti‐Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma

“…After sacrifice, tumors were dissected carefully, washed three times with ice-cold saline to remove extraneous materials and blotted individually on ash-free filter paper. The tumors were chilled on ice and divided into small pieces, which were then wrapped in aluminium foil and stored at −80°C until use [27].…”

“…Also, trypan blue dye was used to distinguish living from dead tumor cells. Only viable tumor cells ≥95% were used for cancer inoculation [27].…”

“…After 1-week adaptation period, the 18 acclimatised experimental mice were injected subcutaneously (sc) in the left thigh with 0.2 mL of ascetic fluid containing 2 × 10 6 viable EAC cells [27]. The animals were randomised and divided into three different groups, each consisting of six mice:…”