title: Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway.
abstract: Kaempferol is a flavonoid compound that has gained importance due to its antitumor properties; however, the underlying mechanisms remain to be fully understood. The present study aimed to investigate the molecular mechanisms of the antitumor function of kaempferol in HepG2 hepatocellular carcinoma cells. Kaempferol was determined to reduce cell viability, increase lactate dehydrogenase activity and induce apoptosis in a concentration‑ and time‑dependent manner in HepG2 cells. Additionally, kaempferol‑induced apoptosis possibly acts via the endoplasmic reticulum (ER) stress pathway, due to the significant increase in the protein expression levels of glucose‑regulated protein 78, glucose‑regulated protein 94, protein kinase R‑like ER kinase, inositol‑requiring enzyme 1α, partial activating transcription factor 6 cleavage, caspase‑4, C/EBP homologous protein (CHOP) and cleaved caspase‑3. The pro‑apoptotic activity of kaempferol was determined to be due to induction of the ER stress‑CHOP pathway, as: i) ER stress was blocked by 4‑phenyl butyric acid (4‑PBA) pretreatment and knockdown of CHOP with small interfering RNA, which resulted in alleviation of kaempferol‑induced HepG2 cell apoptosis; and ii) transfection with plasmid overexpressing CHOP reversed the protective effect of 4‑PBA in kaempferol‑induced HepG2 cells and increased the apoptotic rate. Thus, kaempferol promoted HepG2 cell apoptosis via induction of the ER stress‑CHOP signaling pathway. These observations indicate that kaempferol may be used as a potential chemopreventive treatment strategy for patients with hepatocellular carcinoma.
authors: Department of Hepatitis C and Drug‑Induced Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors: Haiqing
authors: H
authors: Guo
authors: Beijing Institute of Hepatology, Capital Medical University, Beijing 100069, P.R. China.
authors: Feng
authors: F
authors: Ren
authors: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
authors: Li
authors: L
authors: Zhang
authors: Beijing Institute of Hepatology, Capital Medical University, Beijing 100069, P.R. China.
authors: Xiangying
authors: X
authors: Zhang
authors: Beijing Institute of Hepatology, Capital Medical University, Beijing 100069, P.R. China.
authors: Rongrong
authors: R
authors: Yang
authors: Beijing Institute of Hepatology, Capital Medical University, Beijing 100069, P.R. China.
authors: Bangxiang
authors: B
authors: Xie
authors: Beijing Institute of Hepatology, Capital Medical University, Beijing 100069, P.R. China.
authors: Zhuo
authors: Z
authors: Li
authors: Department of Hepatitis C and Drug‑Induced Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors: Zhongjie
authors: Z
authors: Hu
authors: Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors: Zhongping
authors: Z
authors: Duan
authors: Department of Hepatitis C and Drug‑Induced Liver Disease, Beijing Youan Hospital, Capital Medical University, Beijing 100069, P.R. China.
authors: Jing
authors: J
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D044949:Kaempferols / Q000494:pharmacology*; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497249:DDIT3 protein, human; D044949:Kaempferols; D051742:Transcription Factor CHOP; C006552:kaempferol