Apoptosis as a therapeutic strategy for breast cancer: the role of Thymax, a gross thymic extract, in modulating cell death pathways

细胞凋亡 医学 乳腺癌 癌症 体内 肿瘤坏死因子α 时尚 内科学 乳腺肿瘤 程序性细胞死亡 腹腔注射 死亡域 转移 癌症研究 内分泌学 免疫学 生物 半胱氨酸蛋白酶 生物技术 生物化学
作者
Amany Elwakkad,Amina A. Gamal el Din,Mohamed A. Hebishy,Howida S. Abou-Seif
出处
期刊:Egyptian Pharmaceutical Journal (Print) [Medknow]
卷期号:23 (2): 184-198 被引量:1
标识
DOI:10.4103/epj.epj_362_23
摘要

Background Breast cancer is a prevalent disease in women and a leading cause of cancer-related health issues. Thymax, a thymic extract, has shown potential for inducing breast cancer cell apoptosis in vitro . Objective This study aims to investigate how Thymax induces apoptosis and inhibits breast cancer growth and metastasis in vivo . Materials and methods Thymax treatment was divided into five groups: the first group (negative control) − normal rats without tumors. In the second group (positive control), rats were injected subcutaneously in the mammary gland with a single dose of 50 mg/kg b.w. of 7,12-Dimethylbenz(a)anthracene (in 2 ml of corn oil) and allowed to develop tumors for 120 days. Group 3: Thymax was orally administered 6 days a week to tumor-bearing rats (0.4 mg/rat) and continued for 5 weeks. Tumor-bearing rats in group 4 (Thymax injection) received 0.1 ml of Thymax solution through intraperitoneal injection twice weekly for 5 weeks. The last group was Thymax mix (oral and injection); tumor-bearing rats received Thymax solution by dual routes: orally with 0.4 ml six times per week and intraperitoneally with 0.1 ml twice weekly for 5 weeks. Thymax treatment, beginning after 120 days of tumor induction, continued for 5 weeks. Results and conclusion Thymax- induced apoptosis in breast cancer cells by increasing cytochrome c, tumor necrosis factor receptor type 1-associated death domain protein (TRADD), and Fas associated death domain (FADD) levels. It also activated the mitochondrial-dependent pathway with up-regulation of tumor protein gene (P53) expression and cysteine-dependent, aspartate-specific peptidase (caspase-8) activation. Thymax restored normal renal and hepatic cell function and enhanced the immune system by improving total antioxidant levels and inhibiting malondialdehyde levels in treated animals. Histopathological results showed a significant apoptotic effect in the group receiving Thymax injections, demonstrating its capability to induce apoptosis without tumors or atypia in mammary glands. Our findings indicate that Thymax has a significant effect on enhancing tumor cell death and inducing apoptosis in vivo . Thymax may also modulate proapoptotic and antiapoptotic protein expression and activity, regulate the penetrability of the mitochondrial membrane, and release cytochrome c. Furthermore, our findings show that the injection route of Thymax is the fastest and most efficient method to deliver the extract to the tumor site and exert its antitumor effects. These results suggest that Thymax has the potential to be a novel adjuvant in the treatment of breast cancer, as it can enhance the efficacy of conventional therapies and reduce the risk of recurrence and metastasis.

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