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PM · Lens · Methanol Extract of Petasites japonicus Promotes Apoptosis via the MAPK and ROS-dependent Signaling Pathways

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Article · Volume 20, Issue 2 · pp. 389–401

Methanol Extract of Petasites japonicus Promotes Apoptosis via the MAPK and ROS-dependent Signaling Pathways

Na-Ri Choi1, Woo-Gyun Choi1, Min Ji Kwon1, Joon Park2,3, Yun Tai Kim2,3, Min Jae Lee4, Jae-Woo Park5,6, Joo Han Woo7, Byung Joo Kim1

  1. 1Department of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine, Yangsan, REPUBLIC OF KOREA.
  2. 2Division of Food Functionality, Korea Food Research Institute, Wanju-gun, REPUBLIC OF KOREA.
  3. 3Department of Food Biotechnology, Korea University of Science & Technology, Daejeon, REPUBLIC OF KOREA.
  4. 4Department of Veterinary Medicine, College of Veterinary Medicine, Kangwon National University, Chuncheon, REPUBLIC OF KOREA.
  5. 5Department of Gastroenterology, College of Korean Medicine, Kyung Hee University, Seoul, REPUBLIC OF KOREA.
  6. 6Department of Clinical Korean Medicine, Graduate School of Kyung Hee University, Seoul, REPUBLIC OF KOREA.
  7. 7Department of Physiology, Dongguk University College of Medicine, Gyeongju, Republic of Korea.

Abstract

Background: Petasites japonicus (PJ), also known as Butterbur, has a rich history as a traditional healing remedy across numerous countries.Objectives: This study was designed to evaluate the potential anti-cancer properties of the methanol extract derived from PJ (PJE).Materials and Methods: Cell viability was measured with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. Cell cycle analysis, caspase activity assays, western blotting, and reactive oxygen species (ROS) assays were also used to investigate the anticancer effects of PJE on cancer cells.Results: It was shown that PJE inhibited the cell viability of the colon carcinoma cell line Caco-2 (half-maximal inhibitory concentration [IC50]: 268.4 µg/mL), of the hepatocellular carcinoma cell line Hep3B (IC50: 420.2 µg/mL), and of the bladder carcinoma cell line 5637 (IC50: 99.43 µg/mL). Analysis of DNA content indicated an increase in the sub-G1 population of 5637 cells as a result of PJE treatment. Furthermore, PJE caused a reduction in mitochondrial membrane potential and the ratio of Bcl-2 to Bax. Moreover, PJE enhanced the levels of various components involved in the proapoptotic cascade, such as caspase-3, caspase-9, and poly-adenosine diphosphate-ribose polymerase. Moreover, it was observed that PJE modulated mitogen-activated protein kinases (MAPKs) activation and induced an elevation in intracellular production of ROS.Conclusion: These combined results strongly suggest that PJE possesses significant proapoptotic properties as an herbal medicine, acting through ROS-dependent MAPK signaling pathways in bladder cancer cells.

Keywords: Petasites japonicus; cell biology; herbal medicine; cell growth processes; apoptosis; urinary bladder diseases

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