Apigenin as Tumor Suppressor in Cancers: Biotherapeutic Activity, Nanodelivery, and Mechanisms With Emphasis on Pancreatic Cancer

Abstract

Pancreatic cancer is the most lethal malignancy of the gastrointestinal tract. Due to its propensity for early local and distant spread, affected patients possess extremely poor prognosis. Currently applied treatments are not effective enough to eradicate all cancer cells, and minimize their migration. Besides, these treatments are associated with adverse effects on normal cells and organs. These therapies are not able to increase the overall survival rate of patients; hence, finding novel adjuvants or alternatives is so essential. Up to now, medicinal herbs were utilized for therapeutic goals. Herbal-based medicine, as traditional biotherapeutics, were employed for cancer treatment. Of them, apigenin, as a bioactive flavonoid that possesses numerous biological properties (e.g., anti-inflammatory and anti-oxidant effects), has shown substantial anticancer activity. It seems that apigenin is capable of suppressing the proliferation of cancer cells via the induction of cell cycle arrest and apoptosis. Besides, apigenin inhibits metastasis via down-regulation of matrix metalloproteinases and the Akt signaling pathway. In pancreatic cancer cells, apigenin sensitizes cells in chemotherapy, and affects molecular pathways such as the hypoxia inducible factor (HIF), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1). Herein, the biotherapeutic activity of apigenin and its mechanisms toward cancer cells are presented in the current review to shed some light on anti-tumor activity of apigenin in different cancers, with an emphasis on pancreatic cancer.

Multiple Myeloma Inhibitory Activity of Plant Natural Products

“…Apigenin is one of the most abundant flavonoids in plant kingdom and therefore has been the target of various investigations for its use as anticancer agent and for its role in cancer prevention [ 102 , 103 , 104 ]. In these studies, the compound showed anticancer potential via induction of apoptosis and cell cycle arrest as well as the downregulation of matrix metalloproteinases and interaction with miRNAs.…”

MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma

“…Increased glutamine metabolism also protects cells from elevated oxidative stress. Numerous reports have discussed the potential for metabolic stress leading to increased oxidative stress [147,[149][150][151][152][153]. Transcription factor EB (TFEB) has attracted a lot of interest recently for its ability to regulate PDAC growth.…”

Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies

“…Similar to chrysin, apigenin is a potent anti-tumor agent against various cancers including breast cancer, lung cancer and gastric cancer [ 7 ]. Apigenin impairs progression of multiple myeloma cells in a dose-dependent manner.…”

“…Regardless of cancer incidence rate and cell deaths, there have been efforts in developing novel therapeutics for tumor treatment [ 3 , 4 , 5 , 6 ]. Surgery or tumor resection is beneficial in early stages of cancer and when tumor cells diffuse into various tissues in body, it is impossible to eliminate cancer by using surgery [ 7 , 8 ]. Radiotherapy is less invasive compared to surgery, but it has its own problems including side effects and risk of resistance [ 9 ].…”