Abstract
Flavonoids such as naringenin, quercetin, and naringin are known to exhibit anticancer properties. In this study, we examined the effects of these flavonoids on cell viability and apoptotic pathways of cancer cells, either singly or in combination with the type 1 ribosome inactivating protein, Balsamin. Treatment with flavonoids (naringenin, quercetin, and naringin) plus Balsamin for 48 h reduced HepG2 and MCF-7 cell viability, increased the activation of caspase-3 and -8, and induced apoptosis through up-regulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes. Out of the three flavonoids tested, the Balsamin-Naringenin and Balsamin-Quercetin combinations appeared to be most effective compared to the Balsamin-Naringin combination. Balsamin combined with flavonoids also activated endoplasmic reticulum (ER)-stress–mediated apoptosis in breast cancer (MCF-7) cells, which was not activated by Balsamin treatment alone. These experimental results showed that Balsamin combined with flavonoids can reduce HepG2 and MCF-7 cells viability and induce apoptosis, which could be considered as a promising therapeutic approach to sensitize cells to Balsamin treatment, thereby improving its efficacy in breast or liver cancer therapy.
Highlights
Flavonoids are group of polyphenolic compounds found in fruits, vegetables, herbs, cereals, and dairy products (Cook and Samman, 1996)
In subsequent studies on the anti-proliferative effects of Bal on liver (HepG2 and H4IIE) and breast cancer (MCF-7 and BT549) cells, we showed that Bal induced apoptosis in liver cancer cells via increasing the expression of pro-apoptotic markers involved in mitochondrial mediated, death receptor mediated and endoplasmic reticulum (ER)-stress– mediated (GRP78 and CHOP) apoptotic pathways, with no effect observed in the expression of anti-apoptotic genes (Bcl-2 and Bcl-XL)
When HepG2 and MCF-7 cell were co-treated with low dose (0.5 × IC50) of Nir and Bal, the cell viability tended to decrease slightly compared to singly treated groups, the effect was not as prominent as observed with low dose (0.5 × IC50) of Nar or Qu with Bal
Summary
Flavonoids are group of polyphenolic compounds found in fruits, vegetables, herbs, cereals, and dairy products (Cook and Samman, 1996). Flavonoids as a complementary medicine have attracted the attention of researchers due to their diverse pharmacological properties, including antioxidant, antibacterial, antiviral, antitumor, anti-atherosclerosis, antidiabetic, anti-inflammatory, antithrombogenic, hypolipidemic, and neuroprotective effects (Huang et al, 2016) Such biological diversity of flavonoids appears to be associated with their ability to regulate a number of cell signaling cascades, and could play a pivotal role in human health (Williams et al, 2004). A type of flavonoid that is abundantly found in citrus fruits (Puri et al, 2011) It is derived from the hydrolysis of the glycone form of flavanones, such as naringin (Figure 1) (Erlund, 2004).
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