Abstract
Breast cancer is the most common cancer in women worldwide. Hesperidin (Hes) and chlorogenic acid (CA) are traditional medicinal molecules that abundantly exist in natural plants or foods. These compounds have been shown to prevent and suppress various cancers and therefore can be utilized as adjunctive therapies to aid cancer treatment. Here, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays show a greater synergistic inhibitory effect on the growth of breast cancer cells, MCF-7, but not normal breast cells, MCF-10A, than hesperidin or chlorogenic acid alone. We present the possible molecular signaling pathways in MCF-7 cells with or without herbal molecule treatments via proteomic approaches. The data were further analyzed by Ingenuity Pathway Analysis (IPA) and confirmed by quantifying mRNA associated with the estrogen-receptor signaling pathway and mitochondrial functions. We demonstrated that the expression of CYC1, TFAM, ATP5PB, mtATP6, mtDNA, and NRF-1 were decreased upon 12 h treatment, and subsequent ATP production was also significantly decreased at 24 h. These results identified a synergistic effect induced by combinational treatment with hesperidin and chlorogenic acid, which can regulate mitochondria and ATP production through the estrogen receptor pathway in MCF-7 cells. However, none of the treatments induced the generation of reactive oxygen species (ROS), suggesting that ROS likely plays no role in the observed pharmacological activities. Overall, our study sheds light on the adequacy of hesperidin and chlorogenic acid to serve as an adjunctive therapy when co-administrated with chemotherapy drugs in breast cancer patients.
Highlights
Breast cancer is the most prevalent cancer in women worldwide
MTT assay results reveal that 100 μM hesperidin and 350 μM chlorogenic acid caused around 20% and 50% cell death, whereas 30% cell viability was found in the combinational treatment (Figure 1F)
The combination index (CI) of combinational treatment with hesperidin and chlorogenic acid determined by the Chou–Talalay method was 0.76 (Table 2), indicating that the drug combination acts synergistically [11]
Summary
Breast cancer is the most prevalent cancer in women worldwide. In Taiwan, over 10 thousand people were diagnosed with breast cancer in 2013–2016, representing 25% of all new cancer cases in females [1]. While the incidence rate has been increasing slightly by an average of 0.28% annually, breast cancer has the highest incidence rate of all cancers. From 2011–2017, breast cancer was the fourth highest cause of cancer-related deaths, with. 80% of patient having a 5-year relative survival rate [2,3]. Over 2000 breast cancer patients die annually, accounting for more than 10% of total deaths [4]. In line with Taiwan, breast cancer is the fourth leading cause of cancer-related deaths in the US [5]
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