Synthesis of Hydrophobic Propionyl Neohesperidin Ester Using an Immobilied Enzyme and Description of Its Anti-proliferative and Pro-apoptotic Effects on MCF-7 Human Breast Cancer Cells

Abstract

Neohesperidin (NH) is a natural flavonoid glycoside compound with considerable physiological and pharmacological activities. However, its bioavailability is limited due to poor solubility, and few studies have so far attempted improve the solubility and bioavailability of NH. In this study, we structurally modified NH using an immobilized lipase to improve lipophilicity and therefore expand its applicability in lipophilic media as well as enhance its bioavailability in vivo. In addition, we aimed investigated the pro-apoptoptotic activity of this new compound (propionyl neohesperidin ester, PNHE) in MCF-7 breast cancer cells using a variety of cellular assays, including the MTT (3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide assay, assessment of intracellular reactive oxygen species (ROS) levels, and flow cytometry. We successfully synthesized PNHE using immobilized lipases, and the esterification of NH was confirmed by Fourier transform-infrared spectroscopy (FT-IR). Compared to NH, HNPE showed higher anti-proliferative and pro-apoptotic in MCF-7 breast cancer cells, which may be explained by its increased lipophilicity compared to neohesperidin, benefiting to the action of NH on the cancer cell wall. The IC 50 of PNHE for inducing apoptosis of MCF-7 cells was 185.52 µg/mL. PNHE increased both the proportion of cells in Sub-G1 phase and the cellular ROS content, indicating a certain therapeutic effect of HNPE on breast cancer.

Comparison between Traditional Chinese Medicine Constitution and Blood Biochemical Markers Associated with Left and Right Mammary Hyperplasia in Rural Areas of Southwest China

“…The representative compound of qingpi, neohesperidin, a flavonoid glycoside with a strong bitter taste [ 54 ], is also one of the most important natural flavonoid glycosides, with strong anti-inflammatory, anticancer, and cardiovascular protective effects [ 55 ]. Relevant research results show that neohesperidin can significantly inhibit the proliferation of breast cancer (MCF-7 cells) in a dose-dependent manner [ 56 ]. Sinensetin has been shown to significantly inhibit breast cancer resistance protein (ABCG2 or BCRP), thereby improving the clinical efficacy of breast cancer [ 57 ].…”

Antimicrobial and alpha-glucosidase inhibitory flavonoid glycosides from the plant Mussaenda recurvata: in vitro and in silico approaches

“…Six known compounds were elucidated as astragalin (2), 26 isoquercitrin (3), 26 nicotiflorin (4), 27 rutin (5), 27 hesperidin (6), 28 and neohesperidin (7). 29,30 The chemical structures of compounds were elucidated using NMR spectroscopy. The NMR data of 2–7 are shown in Tables S1 and S2.…”

Pharmaceutical characterization and exploration of Arkeshwara rasa in MDA-MB-231 cells

“…Rutin, the former Vitamin P and the natural polyphenolic compound exhibited the third highest peaking in the spectrum. The chemo resistance can be prevented with regulation to Akt/PI3k/mTOR phosphorylation from the conjugated treatment with the compound [ 42 ].…”