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Article

Pogostemon cablin Triggered ROS-Induced DNA Damage to Arrest Cell Cycle Progression and Induce Apoptosis on Human Hepatocellular Carcinoma In Vitro and In Vivo

1
Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
2
Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung 40201, Taiwan
3
Director of Traditional Chinese Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, Taiwan
4
Department of BioIndustry Technology, Da-Yeh University, Changhua 51591, Taiwan
5
Clinical Laboratory, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: José Antonio Lupiáñez, Amalia Pérez-Jiménez, Eva E. Rufino-Palomares and Emerson F. Queiroz
Molecules 2020, 25(23), 5639; https://doi.org/10.3390/molecules25235639
Received: 1 October 2020 / Revised: 27 November 2020 / Accepted: 27 November 2020 / Published: 30 November 2020
(This article belongs to the Special Issue Anticancer Properties of Natural and Derivative Products)
The purpose of the study was to elucidate the anti-hepatoma effects and mechanisms of Pogostemon cablin essential oils (PPa extract) in vitro and in vivo. PPa extract exhibited an inhibitory effect on hepatocellular carcinoma (HCC) cells and was less cytotoxic to normal cells, especially normal liver cells, than it was to HCC cells, exerting a good selective index. Additionally, PPa extract inhibited HCC cell growth by blocking the cell cycle at the G0/G1 phase via p53 dependent or independent pathway to down regulated cell cycle regulators. Moreover, PPa extract induced the FAS-FASL-caspase-8 system to activate the extrinsic apoptosis pathway, and it increased the bax/bcl-2 ratio and reduced ΔΨm to activate the intrinsic apoptosis pathway that might be due to lots of reactive oxygen species (ROS) production which was induced by PPa extract. In addition, PPa extract presented to the potential to act synergistically with sorafenib to effectively inhibit HCC cell proliferation through the Akt/mTOR pathway and reduce regrowth of HCC cells. In an animal model, PPa extract suppressed HCC tumor growth and prolonged lifespan by reducing the VEGF/VEGFR axis and inducing tumor cell apoptosis in vivo. Ultimately, PPa extract demonstrated nearly no or low system-wide, physiological, or pathological toxicity in vivo. In conclusion, PPa extract effectively inhibited HCC cell growth through inducing cell cycle arrest and activating apoptosis in vitro and in vivo. Furthermore, PPa extract exhibits less toxicity toward normal cells and organs than it does toward HCC cells, which might lead to fewer side effects in clinical applications. PPa extract may be developed into a clinical drug to suppress tumor growth or functional food to prevent HCC initiation or chemoprotection of HCC recurrence. View Full-Text
Keywords: hepatocellular carcinoma (HCC); Pogostemon cablin (PPa extract); cell cycle; apoptosis; synergism; chemoprevention hepatocellular carcinoma (HCC); Pogostemon cablin (PPa extract); cell cycle; apoptosis; synergism; chemoprevention
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MDPI and ACS Style

Huang, X.-F.; Sheu, G.-T.; Chang, K.-F.; Huang, Y.-C.; Hung, P.-H.; Tsai, N.-M. Pogostemon cablin Triggered ROS-Induced DNA Damage to Arrest Cell Cycle Progression and Induce Apoptosis on Human Hepatocellular Carcinoma In Vitro and In Vivo. Molecules 2020, 25, 5639. https://doi.org/10.3390/molecules25235639

AMA Style

Huang X-F, Sheu G-T, Chang K-F, Huang Y-C, Hung P-H, Tsai N-M. Pogostemon cablin Triggered ROS-Induced DNA Damage to Arrest Cell Cycle Progression and Induce Apoptosis on Human Hepatocellular Carcinoma In Vitro and In Vivo. Molecules. 2020; 25(23):5639. https://doi.org/10.3390/molecules25235639

Chicago/Turabian Style

Huang, Xiao-Fan, Gwo-Tarng Sheu, Kai-Fu Chang, Ya-Chih Huang, Pei-Hsiu Hung, and Nu-Man Tsai. 2020. "Pogostemon cablin Triggered ROS-Induced DNA Damage to Arrest Cell Cycle Progression and Induce Apoptosis on Human Hepatocellular Carcinoma In Vitro and In Vivo" Molecules 25, no. 23: 5639. https://doi.org/10.3390/molecules25235639

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