Synthetic Genistein Glycosides Inhibiting EGFR Phosphorylation Enhance the Effect of Radiation in HCT 116 Colon Cancer Cells

Abstract

The need to find new EGFR inhibitors for use in combination with radiotherapy in the treatment of solid tumors has drawn our attention to compounds derived from genistein, a natural isoflavonoid. The antiproliferative potential of synthetic genistein derivatives used alone or in combination with ionizing radiation was evaluated in cancer cell lines using clonogenic assay. EGFR phosphorylation was assessed with western blotting. Genistein derivatives inhibited clonogenic growth of HCT 116 cancer cells additively or synergistically when used in combination with ionizing radiation, and decreased EGFR activation. Our preclinical evaluation of genistein-derived EGFR inhibitors suggests that these compounds are much more potent sensitizers of cells to radiation than the parent isoflavonoid, genistein and indicate that these compounds may be useful in the treatment of colon cancer with radiation therapy.

Measurement and correlation of the solubility of genistin in eleven organic solvents from T=(283.2 to 323.2)K

“…Genistin has attracted much attention due to its wide variety of pharmacological activities, such as weak oestrogen activity [1], antioxidant activity [2,3], hemolysis activity and antibacterial activity [4]. It is also considered as an effectual preventive for breast cancer [5], colon cancer [6], osteoporosis [7] and so on. Therefore, Genistin is often used as dietary supplements [8].…”

Andrographolide enhanced radiosensitivity by downregulating glycolysis via the inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 colorectal cancer cells

“…Many studies illustrated that some Chinese herbal monomers, such as curcumin, icariin, and genistein derivatives, enhance radiosensitivity in HT29 and HCT116 cells. 21 – 23 …”

Genistein Inhibits Human Colorectal Cancer Growth and Suppresses MiR-95, Akt and SGK1

“…And oral genistein could also inhibit distant metastasis formation and suppressed neo-angiogenesis in transplanted tumors [6]. In addition, it has been reported that the anti-tumor effects of genistein on CRC also involved with suppression WNT, NF-κB cell Signaling pathway, and modulation of apoptotic gene Bcl-2, Box, EGFR, and ROS [16,25,26,27]. Those findings suggested that genistein possesses effectively anti-cancer effects on CRC without any visible toxicity through the regulation of several signaling pathways.…”

“…Previous study has shown that genistein inhibits human colon cancer cell Caco2 migration, accompanied with decrease of Akt phosphorylation, suggesting that suppression of the Akt signaling pathway may involved in the anti-tumor effects of genistein in CRC [14]. In addition, other tumor-related factors, such as FLT4 [6], estrogen receptor (ER) β [15], and EGFR [16] have also been demostreated to participate in the anti-proliferation and apoptosis-induced effects of genistein on CRC. However, the roles and potential mechanisms of genistein in CRC are still largely unknown.…”