Anticancer Effects of Propionic Acid Inducing Cell Death in Cervical Cancer Cells

Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among whic...

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Published in:Molecules (Basel, Switzerland) Vol. 26; no. 16; p. 4951
Main Authors: Pham, Chau Ha, Lee, Joo-Eun, Yu, Jinha, Lee, Sung Hoon, Yu, Kyung-Rok, Hong, Jaewoo, Cho, Namki, Kim, Seil, Kang, Dukjin, Lee, Soojin, Yoo, Hee Min
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Abstract Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.
AbstractList Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective effects against cervical cancer. The most common SCFAs that are well known include acetic acid, butyric acid, and propionic acid, among which propionic acid (PA) has been reported to induce apoptosis in HeLa cells. However, the mechanism in which SCFAs suppress HeLa cell viability remain poorly understood. Our study aims to provide a more detailed look into the mechanism of PA in HeLa cells. Flow cytometry analysis revealed that PA induces reactive oxygen species (ROS), leading to the dysfunction of the mitochondrial membrane. Moreover, PA inhibits NF-κB and AKT/mTOR signaling pathways and induces LC3B protein levels, resulting in autophagy. PA also increased the sub-G1 cell population that is characteristic of cell death. Therefore, the results of this study propose that PA inhibits HeLa cell viability through a mechanism mediated by the induction of autophagy. The study also suggests a new approach for cervical cancer therapeutics.
Author Pham, Chau Ha
Lee, Sung Hoon
Lee, Soojin
Hong, Jaewoo
Cho, Namki
Yu, Kyung-Rok
Kim, Seil
Yoo, Hee Min
Lee, Joo-Eun
Kang, Dukjin
Yu, Jinha
AuthorAffiliation 6 Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea; cellyu@snu.ac.kr
3 Department of Physiology, Daegu Catholic University School of Medicine, Daegu 42472, Korea; jsmlo@hanmail.net (J.-E.L.); jhong@cu.ac.kr (J.H.)
2 Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Korea; leesoojin@cnu.ac.kr
7 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju 61186, Korea; cnamki@chonnam.ac.kr
8 Convergent Research Center for Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea
1 Biometrology Group, Korea Research Institute of Standards and Science, Daejeon 34113, Korea; pham.ha.chau@hotmail.com (C.H.P.); stapler@kriss.re.kr (S.K.); djkang@kriss.re.kr (D.K.)
9 Department of Bio-Analytical Science, University of Science & Technology (UST), Daejeon 34113, Korea
4 Chemical Kinomics
AuthorAffiliation_xml – name: 1 Biometrology Group, Korea Research Institute of Standards and Science, Daejeon 34113, Korea; pham.ha.chau@hotmail.com (C.H.P.); stapler@kriss.re.kr (S.K.); djkang@kriss.re.kr (D.K.)
– name: 4 Chemical Kinomics Research Center, Korea Institute of Science and Technology, Seoul 02792, Korea; yuj@kist.re.kr
– name: 2 Department of Microbiology and Molecular Biology, Chungnam National University, Daejeon 34134, Korea; leesoojin@cnu.ac.kr
– name: 7 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chonnam National University, Gwangju 61186, Korea; cnamki@chonnam.ac.kr
– name: 5 College of Pharmacy, Chung-Ang University, Seoul 06974, Korea; sunghoonlee@cau.ac.kr
– name: 6 Department of Agricultural Biotechnology, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 08826, Korea; cellyu@snu.ac.kr
– name: 9 Department of Bio-Analytical Science, University of Science & Technology (UST), Daejeon 34113, Korea
– name: 8 Convergent Research Center for Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Korea
– name: 3 Department of Physiology, Daegu Catholic University School of Medicine, Daegu 42472, Korea; jsmlo@hanmail.net (J.-E.L.); jhong@cu.ac.kr (J.H.)
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  surname: Kim
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  givenname: Hee Min
  orcidid: 0000-0002-5951-2137
  surname: Yoo
  fullname: Yoo, Hee Min
  organization: Department of Bio-Analytical Science, University of Science & Technology (UST), Daejeon 34113, Korea
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2021 by the authors. 2021
Copyright_xml – notice: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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Keywords HeLa
short-chain fatty acids
cervical cancer
reactive oxygen species
propionic acid
Language English
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These authors contributed equally to this work.
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Snippet Recent studies found that short-chain fatty acids (SCFAs), which are produced through bacterial fermentation in the gastrointestinal tract, have oncoprotective...
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StartPage 4951
SubjectTerms Acetic acid
AKT protein
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Autophagy
Autophagy - drug effects
Bacteria
Butyric acid
Cell Cycle - drug effects
Cell death
Cell Death - drug effects
Cell viability
Cervical cancer
Cervix
Colorectal cancer
Fatty acids
Female
Fermentation
Flow cytometry
Gastrointestinal system
Gastrointestinal tract
HeLa
HeLa Cells
Homeostasis
Human papillomavirus
Humans
Metabolites
Microbiota
Mitochondria
Mitochondrial Membranes - drug effects
Mitochondrial Membranes - metabolism
NF-kappa B - metabolism
NF-κB protein
Phagocytosis
Probiotics
Propionates - chemistry
Propionates - pharmacology
Propionic acid
Proteins
reactive oxygen species
Reactive Oxygen Species - metabolism
short-chain fatty acids
Signal Transduction - drug effects
TOR protein
Uterine Cervical Neoplasms - metabolism
Uterine Cervical Neoplasms - pathology
Vagina
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Title Anticancer Effects of Propionic Acid Inducing Cell Death in Cervical Cancer Cells
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