Therapeutic Role of Annona muricata Fruit and Bee Venom Against MNU-Induced Breast Cancer in Pregnant Rats and its Complications on the Ovaries

Abstract

Aim: To evaluate the potential therapeutic role of Annona muricata (graviola) fruit and bee venom (BV) against N-methylnitrosourea (MNU)-induced breast cancer in pregnant female rats and complications in the ovaries. Methods: A total of 24 female rats were induced with a single dose of MNU (50 mg/kg body weight). After confirmation of positive tumor marker, female rats were placed with the males for mating. The pregnant rats were randomly divided into four groups (n=6): MNUinduced only (group 1), MNU-induced rats and supplemented with A. muricata 200 mg/kg diet (group 2), MNU-induced and treated with two doses of BV 75 μg/kg (group 3), and MNU-induced and treated with both A. muricata and BV (group 4). Results: In group 1, the breast tissue of mothers revealed pronounced cellular hyperplasia and histopathological signs. Also, the ovarian tissue of mothers and their offspring displayed deleterious histological changes. In groups 2 and 4, histopathological signs and cellular hyperplasia markedly disappeared in breast tissue. However, the histopathological signs induced by MNU in the ovarian tissue reversed to normal in groups 2-4. Also in groups 2-4, levels of serum MMP1, NFκB, and TNFα significantly decreased, and serum caspase 3 significantly increased either in mother rats or their offspring compared to the MNU-alone group. Levels of serum MDA significantly decreased; however, levels of serum antioxidants (CAT and SOD) significantly increased in all groups 2-4 compared to MNU-alone group. Conclusion:A. muricata has a more powerful therapeutic role than BV against MNU-induced breast cancer in rats; however, both have a powerful ameliorative role against ovarian histopathological alterations induced by MNU. Such ameliorative effects of A. muricata and BV are mainly attributed to their antioxidant, anti-inflammatory, and antiproliferative constituents.

Can Bee Venom Be Used as Anticancer Agent in Modern Medicine?

“…Inhibition of colorectal cancer metastases growth in the mice model under the influence of melittin was observed by Rocha et al [79]. Restoration of histological changes in ovarian and breast cancer rat models together with decreasing of serum MMP-1, reduction of NF-κB, and TNF was described by El-Beltagy et al [80].…”

Experimental and computational aspects of bioactive proteins from animal venoms: An insight into pharmacological properties and drug discovery

“…BV alone and in combination with other drugs or solutions had an anti-breast cancer impact (Khamis et al, 2018;Arani et al, 2019;El-Beltagy et al, 2021). In vitro, BV inhibited the growth of MCF7 and T47D cells, while blocking the cell cycle in the G2/M phase.…”

Bee Venom: Composition and Anticancer Properties

“…Moreover, increasing evidence from animal studies indicates the safety of venom doses effective in in vitro studies [47]. Studies done mainly on mice and rats using both whole BV and MEL indicated inhibition of tumors and metastasis growth, suppression of tumor proliferation, inhibition of angiogenesis, reduction of tumor size, and induction of apoptosis [195][196][197][198][199][200]. To the best of our knowledge, currently, there have been no clinical trials on humans that could confirm the clinical effectiveness of bee venom and evaluate the safety of its administration concerning cancer treatment, although there have been several clinical trials either completed or recruiting for other disorders which are registered at https://clinicaltrials.gov/ (Accessed on 5 February 2024).…”