Medical Technology Research Center, Institute of Health Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
Mini Rev Med Chem. 2023;23(14):1461-1478. doi: 10.2174/1389557523666230119110744.
Induction of cell death and inhibition of cell proliferation in cancer have been set as some of the main goals in anti-tumor therapy. Cancer cell resistance leads to less efficient cancer therapy, and consequently, to higher doses of anticancer drugs, which may eventually increase the risk of serious side effects in normal tissues. Apigenin, a nature-derived and herbal agent, which has shown anticancer properties in several types of cancer, can induce cell death directly and/or amplify the induction of cell death through other anti-tumor modalities. Although the main mechanism of apigenin in order to induce cell death is apoptosis, other cell death pathways, such as autophagic cell death, senescence, anoikis, necroptosis, and ferroptosis, have been reported to be induced by apigenin. It seems that apigenin enhances apoptosis by inducing anticancer immunity and tumor suppressor genes, like p53 and PTEN, and also by inhibiting STAT3 and NF-κB signaling pathways. Furthermore, it may induce autophagic cell death and ferroptosis by inducing endogenous ROS generation. Stimulation of ROS production and tumor suppressor genes, as well as downregulation of drug-resistance mediators, may induce other mechanisms of cell death, such as senescence, anoikis, and necroptosis. It seems that the induction of each type of cell death is highly dependent on the type of cancer. These modulatory actions of apigenin have been shown to enhance anticancer effects by other agents, such as ionizing radiation and chemotherapy drugs. This review explains how cancer cell death may be induced by apigenin at the cellular and molecular levels.
诱导细胞死亡和抑制细胞增殖已被设定为抗肿瘤治疗的一些主要目标。癌细胞的耐药性导致癌症治疗效果不佳，因此需要更高剂量的抗癌药物，这最终可能会增加正常组织发生严重副作用的风险。芹黄素是一种天然存在的草药制剂，已在多种类型的癌症中显示出抗癌特性，它可以直接诱导细胞死亡和/或通过其他抗肿瘤方式放大细胞死亡的诱导。尽管芹黄素诱导细胞死亡的主要机制是细胞凋亡，但其他细胞死亡途径，如自噬性细胞死亡、衰老、失巢凋亡、坏死性凋亡和铁死亡，也已被报道由芹黄素诱导。芹黄素似乎通过诱导抗癌免疫和肿瘤抑制基因（如 p53 和 PTEN），以及抑制 STAT3 和 NF-κB 信号通路，增强细胞凋亡。此外，它可能通过诱导内源性 ROS 产生来诱导自噬性细胞死亡和铁死亡。刺激 ROS 产生和肿瘤抑制基因，以及下调耐药介质，可能会诱导其他细胞死亡机制，如衰老、失巢凋亡和坏死性凋亡。似乎每种类型的细胞死亡的诱导都高度依赖于癌症的类型。芹黄素的这些调节作用已被证明可以增强其他药物（如电离辐射和化疗药物）的抗癌作用。这篇综述解释了芹黄素如何在细胞和分子水平上诱导癌细胞死亡。
