Anticancer Effects and Molecular Mechanisms of Apigenin in Cervical Cancer Cells

Abstract

Cervical cancer is the fourth most frequent malignancy in women. Apigenin is a natural plant-derived flavonoid present in common fruit, vegetables, and herbs, and has been found to possess antioxidant and anti-inflammatory properties as a health-promoting agent. It also exhibits important anticancer effects in various cancers, but its effects are not widely accepted by clinical practitioners. The present study investigated the anticancer effects and molecular mechanisms of apigenin in cervical cancer in vitro and in vivo. HeLa and C33A cells were treated with different concentrations of apigenin. The effects of apigenin on cell viability, cell cycle distribution, migration potential, phosphorylation of PI3K/AKT, the integrin β1-FAK signaling pathway, and epithelial-to-mesenchymal transition (EMT)-related protein levels were investigated. Mechanisms identified from the in vitro study were further validated in a cervical tumor xenograft mouse model. Apigenin effectively inhibited the growth of cervical cancer cells and cervical tumors in xenograft mice. Furthermore, the apigenin down-regulated FAK signaling (FAK, paxillin, and integrin β1) and PI3K/AKT signaling (PI3K, AKT, and mTOR), inactivated or activated various signaling targets, such as Bcl-2, Bax, p21cip1, CDK1, CDC25c, cyclin B1, fibronectin, N-cadherin, vimentin, laminin, and E-cadherin, promoted mitochondrial-mediated apoptosis, induced G2/M-phase cell cycle arrest, and reduced EMT to inhibit HeLa and C33A cancer cell migration, producing anticancer effects in cervical cancer. Thus, apigenin may act as a chemotherapeutic agent for cervical cancer treatment.

GC-MS analysis and invitro cytotoxic activity of Ocimum basilicum (Lamiaceae) volatile oil and active fraction composed majorly of estragole

“…The use of medicinal herbs for cancer treatment alongside conventional therapies has received increasing recognition due to their anticancer potential [3]. The benefits of medicinal herbs in tumor treatment have been attributed to their phytochemical content [4][5][6] which include flavonoids, phenolic acids, and essential oils. Such bioactive compounds have been found to be potent immunomodulators, with the potential to minimize negative impacts from cancer treatment [2].…”

Deciphering the modulatory role of apigenin targeting oncogenic pathways in human cancers

“…Apigenin inhibited the growth of C33A tumor xenografts in a cervical tumor xenograft mouse model. Inactivating or activating a number of signaling targets, including Bcl-2, Bax, p21cip1, CDK1, CDC25c, cyclin B1, fibronectin, N-cadherin, vimentin, laminin, and E-cadherin, the apigenin decreased FAK signaling (FAK, paxillin, and integrin 1) and PI3K/AKT signaling (PI3K, AKT, and mTOR) (Chen et al, 2022). Carcinogenesis is a multistage process that affects both the genetic code and the epigenome and is responsible for the initiation, promotion, and progression of cancer.…”

Apigenin in cancer therapy: Prevention of genomic instability and anticancer mechanisms

“…Apigenin has been used in several clinical trial studies for non-cancer diseases such as Alzheimer's, osteoarthritis and depression, among others, the results of which have revealed propitious outcomes regarding the safety and clinical effects in patients. 156 The chemoprotective and anticancer effects of apigenin in cancer patients are required to be thoroughly scrutinized in the future clinical trial studies. A clinical trial study (NCT03526081) is ongoing to evaluate the absorption, metabolism and excretion of apigenin in healthy people.…”

“…To begin with, it is of great importance to determine a safe dose of apigenin for cancer patients. Apigenin has been used in several clinical trial studies for non‐cancer diseases such as Alzheimer's, osteoarthritis and depression, among others, the results of which have revealed propitious outcomes regarding the safety and clinical effects in patients 156 . The chemoprotective and anticancer effects of apigenin in cancer patients are required to be thoroughly scrutinized in the future clinical trial studies.…”