Maryam Mohsenikia1, Baharak Farhangi2, Ali Mohammad Alizadeh3, Hamid Khodayari3, Saeed Khodayari4, Vahid Khori3, Yasaman Arjmand Abbassi3, Milica Vesovic5, Ali Soleymani1, Farhood Najafi6. 1. Dezful University of Medical Sciences, Dezful, Iran. 2. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: aalizadeh@sina.tums.ac.ir. 3. Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran. 4. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran. 5. Department of Mathematics, Statistic, and Computer Science, University of Illinois at Chicago, USA. 6. Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran.
Abstract
AIMS: Our previous studies showed that alpha-solanine can inhibit tumor growth in cell culture and animal models of breast cancer. However, solanine is insoluble in common solvents; therefore, we developed a special nanoparticle with high-capacity solubility. The present study is aimed to deliberate the therapeutic effects of dendrosomal solanine (DNS) on a metastatic breast tumor in vitro and in vivo. MAIN METHODS: After DNS preparation and dosing procedures, forty-five mice were equally divided into five groups to investigate the anti-metastatic effects of DNS on mammary tumor-bearing mice. KEY FINDINGS: Compared to solanine, DNS significantly suppressed the proliferation of 4 T1 cells in a dose- and time-dependent manner. DNS showed a remarkable safety rate of up to 10mg/kg. A significant decrease in white blood-cell count was seen at 20mg/kg DNS in comparison with control animals. Mice treated with DNS had smaller tumor volume (mm(3)) in comparison with control and solanine groups. Moreover, the incidence of the breast tumor metastases was about 67% in the control animals, where as solanine and DNS 1mg/kg were about 22% and 0%, respectively. Furthermore, the number of metastases per mouse varied from one to three. The tissues of tumor, brain, liver, spleen, and lung showed higher expression levels of Bcl-2 but lower expression levels of Bax, MMP-2, MMP-9, mTOR, and Akt in DNS-treated mice than control and solanine groups. SIGNIFICANCE: The findings suggest that DNS has a more impactful therapeutic effect than solanine on 4 T1-induced breast tumorigenesis via influencing the tissue microenvironment.
AIMS: Our previous studies showed that alpha-solanine can inhibit tumor growth in cell culture and animal models of breast cancer. However, solanine is insoluble in common solvents; therefore, we developed a special nanoparticle with high-capacity solubility. The present study is aimed to deliberate the therapeutic effects of dendrosomal solanine (DNS) on a metastatic breast tumor in vitro and in vivo. MAIN METHODS: After DNS preparation and dosing procedures, forty-five mice were equally divided into five groups to investigate the anti-metastatic effects of DNS on mammary tumor-bearing mice. KEY FINDINGS: Compared to solanine, DNS significantly suppressed the proliferation of 4 T1 cells in a dose- and time-dependent manner. DNS showed a remarkable safety rate of up to 10mg/kg. A significant decrease in white blood-cell count was seen at 20mg/kg DNS in comparison with control animals. Mice treated with DNS had smaller tumor volume (mm(3)) in comparison with control and solanine groups. Moreover, the incidence of the breast tumor metastases was about 67% in the control animals, where as solanine and DNS 1mg/kg were about 22% and 0%, respectively. Furthermore, the number of metastases per mouse varied from one to three. The tissues of tumor, brain, liver, spleen, and lung showed higher expression levels of Bcl-2 but lower expression levels of Bax, MMP-2, MMP-9, mTOR, and Akt in DNS-treated mice than control and solanine groups. SIGNIFICANCE: The findings suggest that DNS has a more impactful therapeutic effect than solanine on 4 T1-induced breast tumorigenesis via influencing the tissue microenvironment.