Potential Antitumor Effect of α-Mangostin against Rat Mammary Gland Tumors Induced by LA7 Cells

Abstract

In this study, the chemotherapeutic effect of α-mangostin (AM) was assessed in rats injected with LA7 cells. Rats received AM orally at 30 and 60 mg/kg twice a week for 4 weeks. Cancer biomarkers such as CEA and CA 15-3 were significantly lower in AM-treated rats. Histopathological evaluations showed that AM protects the rat mammary gland from the carcinogenic effects of LA7 cells. Interestingly, AM decreased lipid peroxidation and increased antioxidant enzymes when compared to the control. Immunohistochemistry results of the untreated rats showed abundant PCNA and fewer p53-positive cells than AM-treated rats. Using the TUNEL test, AM-treated animals had higher apoptotic cell numbers than those untreated. This report revealed that that AM lessened oxidative stress, suppressed proliferation, and minimized LA7-induced mammary carcinogenesis. Therefore, the current study suggests that AM has significant potential for breast cancer treatment.

Keywords: LA7 cells; antioxidant; apoptosis; immunohistochemistry; mammary cancer; α-mangostin.

Figure 1

Chemical structure of α-mangostin (AM).

Figure 2

The effect of treatments on animal tumor volume (mm³) at 0, 7, 14, and 28 days compared to the control groups. Each value represents mean ± S.D. of given number of animals (n = 5), Values are statistically significant at * p < 0.05.

Figure 3

Histopathological photomicrograph of (A) Normal mammary gland before experimental cancer induction; note well differentiated ductal structure. Black arrow refer to normal well differentiated ductal structure. (B) Mammary gland after experimental tumor induction; note poorly differentiated ductal and tubular structures with variation in cellular nuclear sizes (UT). Note insert (left bottom corner) showing neovascularization disrupted tubular structure and high mitotic index. (C) Mammary gland treated with low dose after experimental cancer induction. Note reorganization of mammary tubular structure (MR) demarcated by muscle from tubular adenocarcinoma (AC). Note insert (left bottom corner) showing reorganization of tubular structure and neovascularization disrupted tubular structure. (D) Mammary gland treated with high dose after experimental cancer induction. Note reorganization of mammary tissue (R) interspersed with tubular adenocarcinoma (TA) with extensive necrosis and hyaline deposition in the connective tissue. Note insert (left bottom corner) showing organization of tubular structure and extensive necrosis of the connective tissue. (E) Mammary gland treated with TAM after experimental mammary tumor induction, showing ductal reorganization (RT). Note neovascularization, congestion, necrosis, and reorganization of mammary tissue interspersed with adenocarcinoma (insert). (F) Mammary gland treated with AM 60 mg/kg alone showing apparently normal appearance of tissue with well-differentiated ductal structure (Bar = 50 µm, H&E).

Figure 4

In situ TdT-mediated dUTP nick-end labeling (TUNEL assay) in breast tissue of rats. (A) Normal section showing absence of apoptotic cells. (B) TUNEL staining in (MTC group) section showing aggressive cell proliferation without apoptosis. (C) Cancerous section treated with 30 mg/kg body wt. AM showing numerous TUNEL-positive cells. (D) Cancerous section treated with 60 mg/kg body wt. AM showing frequent TUNEL-positive cells among treatment groups. (E) Cancerous section treated with 10 mg/kg body wt. of TAM showing the most frequent TUNEL-positive cells among treatment groups. (F) For an amount of 60 mg/kg AM alone no signs of apoptosis were noted on these sections (Bar = 20 µm).

Figure 5

Depicts immunoexpression of PCNA in (A) Normal control rats (no expression), (B) MTC group without treatment rats (over expression) with strong diffuse intensity, (C) (MT + AM-LD)-treated rats (down-regulated) with strong multifocal intensity, (D) (MT + 60 mg/kg AM-HD) treated rats (down-regulated) strong focal intensity, (E) (MT + 10 mg/kg TAM) down-regulation with strong focal intensity. (F) AM-HD 60 mg/kg alone treated rats (expression not detectable). Brown staining indicates positive cells (20× magnifications).

Figure 6

Depicts immunoexpression of p53 in (A) Normal control rats (weak expression), (B) MTC group without treatment rats (weak expression), (C) (MT + AM-LD)-treated rats (up-regulated) with strong multifocal intensity, (D) (MT + AM-HD)-treated rats (up-regulated) with strong focal intensity, (E) (MT + 10 mg/kg TAM) up-regulated with strong multifocal intensity, (F) AM 60 mg/kg alone treated rats (weak expression). Brown staining indicates positive cells (20× magnifications).