Hesperidin Inhibits Lung Cancer In Vitro and In Vivo Through PinX1

Abstract

New drugs or active leads with high efficiency and low toxicity are needed in the treatment of lung cancer. Natural products are an important source of anti-tumor drugs. At present, there are many molecular-targeted anti-tumor drugs derived from natural products or their derivatives for tumor treatment or in clinical trials. Hesperidin is a flavanone isolated from the Rutaceae plant lime Citrus aurantium L. or Citrus sinensis Osbeck. It has been considered to inhibit cancer cell viability in vitro. However, the effect of hesperidin on lung cancer and its underlying mechanism remain unclear. In this study, we found that the pinX1 expression level is closely related to overall survival and plays an important role in regulating lung cancer cell proliferation, migration, invasion, and senescence. More importantly, hesperidin significantly increased pinX1 protein expression, and knockdown pinX1 by its specific siRNA blocked the protective effects of hesperidin. Moreover, we also assessed that hesperidin at 100 mg/kg is safe in vivo. These findings showed that hesperidin is a potential therapeutic candidate for preventing the progression of lung cancer.

A Two-Step Approach to Orange Peel Waste Valorization: Consecutive Extraction of Pectin and Hesperidin

“…These results follow Flick's second law, which predicts an equilibrium of solute concentration between matrix and solvent. Our findings are also supported by another study, which analyzed the effect of different extraction times (10,20,30,40,50, and 60 min) on hesperidin yields at 60% ethanol concentration, 60 • C, and 30 mL/g dry sample [51]. After 30 min of extraction, they verified that there was no statistically significant difference between yields.…”

“…This citrus flavanone has also been researched as a possible antiviral agent against the Influenza A virus [14], Hepatitis B virus [15], and SARS-CoV-2 [16]. Moreover, it has been studied as an anti-obesity [17], neuroprotective [18,19], anti-cancer [20], and anti-aging agent [21,22]. In the food industry, hesperidin derivatives are commonly used as food additives to enhance the antioxidant and antimicrobial activities of active packaging films instead of hesperidin, given its limited water solubility, bitterness, and poor oral bioavailability [23,24].…”

TRIB3 promotes malignancy of head and neck squamous cell carcinoma via inhibiting ferroptosis

“…In this regard, a novel TRIB3 inhibitor, hesperidin, was developed as a potential therapeutic agent for HNSCC. Hesperidin, a natural ingredient with effectiveness against different cancer types and a history of use in traditional Chinese medicine, demonstrated efficacy against tumor progression in both in vitro and in vivo studies [ 40 – 43 ]. When treated with hesperidin, HNSCC cells exhibited a pro-ferroptosis phenotype, closely resembling TRIB3-knockdown effects.…”

Recent understanding of the mechanisms of the biological activities of hesperidin and hesperetin and their therapeutic effects on diseases

“… [ 58 ] [ 179 ] Lung cancer Hsd Cisplatin-induced A549 cells Decrease the expression of P-gp and increased the intracellular accumulation of the P-gp substrate, rhodamine 123 [ 180 ] Lung cancer Hsd LLC cells Lung carcinoma mice Increase pinX1 protein expression. [ 181 ] Gastric cancer Hsd MNNG-induced rats Activate autophagy and the PI3K/AKT pathway. [ 182 ] Esophageal cancer Hst Eca109 cells Human xenograft tumor nude mice Depletion of GSH, accumulation of ROS, increase of cleaved caspase-9 and cleaved caspase-3 [ 183 ] Ehrlich ascites carcinoma Hsd Ehrlich ascites carcinoma (EAC) mice Down-regulate Bcl2 and Stimulate Caspase3 and Bax genes expression [ 184 ] Liver cancer Hsd DEN/CCl4-induced rats Activate Nrf2/ARE/HO-1 and PPARγ pathways.…”