Potentiation of the Effect of Lonidamine by Quercetin in MCF-7 human breast cancer cells through downregulation of MMP-2/9 mRNA Expression

Abstract

Combination therapies are becoming increasingly important to develop an effective treatment in cancer. Lonidamine is frequently used in cancer treatment, but it's often preferred to be used in combination with other drugs because of its side effects. In the present study, the effi cacy of the combination of lonidamine with quercetin, a fl avonoid of natural origin, on human MCF-7 breast cancer cells was evaluated. The results showed that the combined use of the compounds signifi cantly increased cytotoxicity compared to administration alone (p<0.0001). In addition, while lonidamine induced a cell cycle arrest in the G2/M phase, administration of quercetin and its combination with lonidamine arrested the cell division at S point, indicating the synergistic strength of quercetin on cytotoxicity. The combination of quercetin and lonidamine signifi cantly induced apoptosis of MCF-7 cells (p<0.0001) and increased caspase levels (p<0.0001). In this study, the combination of quercetin and lonidamine has been evaluated for the fi rst time and the combination treatment decreased MMP-2/-9 mRNA expression more potently than the effects of the compounds alone. The results showed that lonidamine was more effective when combined with quercetin, and their combination may be a candidate for a novel strategy of treatment for breast cancer.

Investigating the mechanism of Xian-ling-lian-xia-fang for inhibiting vasculogenic mimicry in triple negative breast cancer via blocking VEGF/MMPs pathway

“…Quercetin regulated the immunomodulatory function through the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells [ 42 ]. Quercetin could inhibit the proliferation and invasion of breast cancer cells by downregulating the expression of MMP2 and MMP9 [ 43 ]. Kaempferol suppressed proliferation and induced cell cycle arrest, apoptosis, and DNA damage in MDA-MB-231 cells [ 44 ].…”

Natural Melanogenesis Inhibitor, Antioxidant, and Collagen Biosynthesis Stimulator of Phytochemicals in Rice Bran and Husk Extracts from Purple Glutinous Rice (Oryza sativa L. cv. Pieisu 1 CMU) for Cosmetic Application

“…In addition, published studies revealed the inhibitory effect of quercetin on radical production and the expression of MMP [ 60 ]. Along with previous works, quercetin could reduce the expression of MMP-2 based on the suppression of nuclear factor-kB (NF-kB) [ 61 ] or modulation of superoxide dismutase (SOD) activity [ 62 ]. Several studies demonstrated that the quercetin compound found in plant extracts like Oenothera biennis [ 63 ] and Magnolia officinalis [ 64 ] can inhibit MMP-2 secretion and be used as an anti-aging agent.…”

Quercetin induced HepG2 cells apoptosis through ATM/JNK/STAT3 signaling pathways

“…In terms of antiallergy, quercetin alleviates the inflammatory response of allergic conjunctivitis by inhibiting the membrane-associated protein tyrosine kinase (Lyn) (Ding et al, 2020). In previous studies, the anti-tumor activity of quercetin was reported (Azeem et al, 2022), which inhibits tumor cell proliferation and downregulates tumor protein expression (Ozkan and Bakar-Ates, 2020;Song et al, 2020a). In vitro experiments showed that quercetin alone can induce apoptosis of 13 hepatocellular carcinoma cell lines.…”

“…Quercetin also potentially has anti-tumor properties (Tang et al, 2020). It inhibits the proliferation of colon cancer (Lin et al, 2020) and can downregulate the expression of MMP-2/-9 protein to restrict the hyperplasia of breast cancer cells named MCF-7 (Ozkan and Bakar-Ates, 2020). Song et al (2020a) found that the PI3K/Akt/mTOR signaling pathway could be blocked by quercetin for curing human prostate cell carcinoma PC-3 cells.…”