Hesperidin induces apoptosis and G0/G1 arrest in human non-small cell lung cancer A549 cells

Abstract

Lung cancer has high incidence and mortality rates worldwide. In the present study, the mechanisms by which hesperidin decreases the viability and induces the apoptosis of human non-small cell lung cancer (NSCLC) A549 cells were investigated. Initially, MTT and flow cytometric assays were performed to evaluate the effects of hesperidin on the viability and apoptosis of A549 cells and human normal lung epithelial BEAS-2B cells. The results revealed that hesperidin has no negative effects on the human normal lung epithelial BEAS-2B cells and the viability of cells treated with various concentrations of hesperidin was inhibited in a time- and dose-dependent manner compared with the control groups. Subsequently, the expression levels of proteins involved in the mitochondria-associated apoptotic pathway were studied by western blot analysis. Hesperidin was identified to induce A549 cell apoptosis by downregulating the levels of B-cell lymphoma-2 (Bcl-2) and Bcl extra large protein and simultaneously upregulating the levels of Bcl-2-associated X protein, BH3 interacting-domain death agonist (Bid), tBid, cleaved caspase-9, cleaved caspase-3 and cleaved poly(adenosine diphosphate ribose)polymerase. The effect of hesperidin on the cell cycle was assessed by flow cytometry. Hesperidin was observed to cause G0/G1 arrest of A549 cells by decreasing the expression of cyclin D1 and increasing the expression of p21 and p53. In summary, it was demonstrated that hesperidin induced apoptosis through the mitochondrial apoptotic pathway and induced G0/G1 arrest in human NSCLC A549 cells. Therefore, hesperidin may be developed as a potential therapeutic drug for the treatment of NSCLC.

Anti‐carcinogenic effect of hesperidin against renal cell carcinoma by targeting COX‐2/PGE2 pathway in Wistar rats

“…Currently, research is being carried out to explore the pharmacological properties of herbal compounds and their preventive effect in many diseases. Hesperidin has been well documented for its multiple biological properties and its role in attenuating oxidative stress, toxicity, and cancer induced by various toxicants . In this context, we designed our study to evaluate the preventive effects of hesperidin on DEN initiated and Fe‐NTA promoted renal carcinogenesis by studying its molecular targets.…”

Inhibitory Effect of Hesperidin on the Expression of Programmed Death Ligand (PD-L1) in Breast Cancer

“…Previous reports have shown that hesperidin is nontoxic to normal cells, but it is an effective anticancer agent against several types of cancer including bladder cancer, prostate cancer, breast cancer, and hepatocellular carcinoma [6][7][8]. It has already been reported that hesperidin induces anticancer activity through the promotion of apoptosis [9]. A recent report showed that hesperidin also inhibits epithelial-mesenchymal transition (EMT) and the expression of members of the MMP family, and thereby inhibiting cell invasion and contributing to its anticancer activity [10].…”

Tanshinone I induces cell apoptosis by reactive oxygen species-mediated endoplasmic reticulum stress and by suppressing p53/DRAM-mediated autophagy in human hepatocellular carcinoma

“…It is well known that cell cycle progression is dependent on the activity of cyclin-dependent kinase complexes (cyclin-CDKs). Downregulation of cyclin D1 may arrest the cell cycle at the G0/G1 phase [20,21]. p21, a broad-spectrum CDK inhibitor, has been demonstrated to promote cell cycle arrest by inhibiting the activity of various cyclin-CDK complexes [22,23].…”