Research Article: Antimutagenic and Synergistic Cytotoxic Effect of Cisplatin and Honey Bee Venom on 4T1 Invasive Mammary Carcinoma Cell Line

Date Published: January 29, 2019

Publisher: Hindawi

Author(s): Faranak Shiassi Arani, Latifeh Karimzadeh, Seyed Mohammad Ghafoori, Mohammad Nabiuni.


Honey bee venom (HBV) has various biological activities such as the inhibitory effect on several types of cancer. Cisplatin is an old and potent drug to treat most of the cancers. Our aim in the present study was to determine antimutagenic and cytotoxic effects of HBV on mammary carcinoma, exclusively and in combination with cisplatin.

In this study, 4T1 cell line was cultured in RPMI-1640 with 10% fetal bovine serum (FBS), at 37°C in humidified CO2 incubator. The cell viabilities were examined by the MTT assay. Also, HBV was screened‏ for its antimutagenic activity via the Ames test. The results were assessed by SPSS software version 19 and one-way ANOVA method considering p < 0.05 level of significance. The results showed that 6 mg/ml of HBV, 20 μg/ml of cisplatin, and 6 mg/ml HBV with 10 μg/ml cisplatin could induce approximately 50% of 4T1 cell death. The concentration 7 mg/ml of HBV with of 62.76% inhibitory rate showed the highest antimutagenic activity in comparison with other treatment groups. The MTT assay demonstrated that HBV and cisplatin could cause cell death in a dose-dependent manner. The cytotoxic effect of cisplatin also promoted by HBV. Ames test outcomes indicated that HBV could act as a significant mutagenic agent. The antimutagenic activity of HBV was increased considerably in the presence of S9 mix. Therefore, our findings have revealed that HBV can enhance the cytotoxic effect of cisplatin drug and its cancer-preventing effects.

Partial Text

Breast carcinoma is a common cancer and the most common malignancy among women in the industrialized countries for the last decades. Breast cancer originates from the breast tissue and uncontrolled growth of the inner lining of the milk ducts or lobules [1]. Breast cancer is the most commonly diagnosed cancer and the primary cause of cancer death among worldwide females [2]. Several studies have shown that breast carcinoma mostly occurs in similar structures of the breast, and these structures are the origin site of ductal carcinoma. Approximately 1-2 years after the onset of the first menstrual period, lobule formation is started. There is a gradual process for mammary gland, for which it needs several years. Parous women, particularly women who have full-term pregnancy experience at young age, have full lobular differentiation in breast structure [3]. The most risk factors for breast cancer have been estimated and studied such as diet, oral contraception, and postmenopausal substituent treatment with estrogen, breast irradiation, and environment [4].

Breast cancer is the most prevalent cancer among women of developed countries, and its incidence has been expanding worldwide [16]. The cytotoxic chemotherapy is used to cure the early and late stages of most cancers in the recent decade [17]. In the 1970s, findings about the anticancer effect of Cisplatin lead to a revolution in the clinical chemotropic agent [18]. Our objectives included examining the cytotoxic and antimutagenic effects of HBV and cisplatin on the mouse mammary carcinoma 4T1 cell.

According to our results in the present research, we assessed that HBV as a natural product has cytotoxic effects on the mouse mammary carcinoma 4T1 cell line. Cisplatin as a chemotropic drug to cure several types of cancer has cytotoxic effects on the 4T1 cell line. However, in combination with HBV, its cytotoxic effect is promoted, and it can be more effective in nonlethal dosages. Furthermore, antimutagenic and anticancer activities of HBV were seen in the presence of the S9 metabolic activation system in all concentrations of HBV. It will be an excellent perspective to innovate approaches to prevent and treat some features of cancer.




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