Total Flavone Content of Cydonia oblonga Miller Inhibits Proliferation and Migration of Renal Carcinoma Cells by Inhibiting the S1PR2/FAK Pathway

Author:

Nuer Muhadaisi1,Khan Nawaz1,Zhang Bentuo2,Abdurousuli Kayisairer1,Yin Houqing2,Wang Dan2,Simayi Jimilihan1,Maihemuti Nulibiya1,Talihati Ziruo1,Hailati Sendaer1,Wang Zequn2,Han Mengyuan1,Wumaier Ainiwaer1,Ribai Yan3,Zhou Wenting1ORCID,Pan Yan2ORCID

Affiliation:

1. Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, No. 393, Xinyi Road, Urumqi 830011, Xinjiang, China

2. Department of Pharmacology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100191, China

3. School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

Abstract

Cydonia oblonga Miller (C. oblonga) is known for its beneficial properties for health since ancient times. C. oblonga has also been shown to possess antihemolytic, antidiabetic, and antilipoperoxidation, as well as lipid-lowering properties. Modern research has shown that C. oblonga also possess antitumor effects. However, studies have not reported whether its main compounds inhibit renal cell carcinoma (RCC) development and progression. We found the inhibitory effect of total flavone of C. oblonga (TFCOM) in RCC cells through in vitro screening tests. The molecular mechanism of this effect is still unknown. Therefore, molecular docking combined with network pharmacological methods was used in order to clarify the molecular mechanisms of TFCOM anticancer effects. TFCOM showed potent inhibitory effects on the proliferation and migration of 786-O and Renca cells. Hoechst 33342 staining test results indicated that TFCOM’s cell growth inhibition in RCC cells may be mediated through apoptosis. It may significantly influence S1PR2/FAK, WNT/β-catenin, and PI3K/AKT/mTOR signaling pathways that can regulate a series of cellular activities and can participate in the processes of cell proliferation, migration, and apoptosis. We conclude that TFCOM has antitumor activity against kidney cancer. It may induce apoptosis and inhibitory effects on cell proliferation and migration through S1PR2/FAK, WNT/β-catenin, and PI3K/AKT/mTOR signal pathways. TFCOM might be a potential anticancer drug to be further developed for human kidney cancer therapy. In recent years, many synthetic drugs with anticancer effects have the disadvantages of high price and side effects. Thus, the development of anticancer drugs from natural resources has its application value. Our results suggest that TFCOM, as a natural product, has multiple target effects, and it may act through proteins and receptors such as FAK and S1PR2, thereby affecting the activation of downstream proteins and inhibiting the occurrence and development of renal cancer cells.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Cell Biology,Pharmacology,Food Science,Biophysics

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