Torilis japonica extract-generated intracellular ROS induces apoptosis by reducing the mitochondrial membrane potential via regulation of the AMPK-p38 MAPK signaling pathway in HCT116 colon cancer.
Torilis japonica extract (TJE) has been reported to possess diverse medicinal properties including anti‑inflammatory and antibacterial activities. However, the precise mechanism of its anticancer effect is not understood. Thus, we evaluated the apoptotic effects of TJE and examined its underlying molecular mechanisms in HCT116 colorectal cancer cells. Our results show that TJE induces apoptosis through the generation of intracellular reactive oxygen species (ROS), and that it regulates the mitochondrial outer membrane potential via the AMPK/p38 MAPK signaling pathway. Importantly, ~50% of cancer cells have p53 mutations. Thus, the ability to induce apoptosis in a p53-independent manner would be of great value in cancer treatment. Our results show that not only does TJE regulate the AMPK/p38 signaling pathway, but it induces apoptosis in cells in which p53 has been knocked down using siRNA. Moreover, as in in vitro studies, TJE induced apoptosis and regulated apoptosis related-proteins in an HCT 116 xenograft model. Taken together, our results demonstrate that TJE, a natural compound that may provide a substitute for chemotherapeutic drugs, has potential as an anticancer agent.
Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University, Yuseong-gu, Daejeon 305-811, Republic of Korea.
Guen Tae
GT
Kim
Pharma-gene Inc., Yuseong-gu, Daejeon 305-811, Republic of Korea.
Se Hee
SH
Lee
Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University, Yuseong-gu, Daejeon 305-811, Republic of Korea.
Young Min
YM
Kim
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D051379:Mice; D009154:Mutation; D010936:Plant Extracts / Q000008:administration & dosage* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D064028:Tracheophyta / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53