Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway

Currently, therapies for treating oral cancer have various side effects; therefore, research on treatment methods employing natural substances is being conducted. This study aimed to investigate piperine-induced apoptosis and autophagy in HSC-3 human oral cancer cells and their effects on tumor grow...

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Main Authors: Eun-Ji Han, Eun-Young Choi, Su-Ji Jeon, Sang-Woo Lee, Jun-Mo Moon, Soo-Hyun Jung, Ji-Youn Jung
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/18/13949
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author Eun-Ji Han
Eun-Young Choi
Su-Ji Jeon
Sang-Woo Lee
Jun-Mo Moon
Soo-Hyun Jung
Ji-Youn Jung
author_facet Eun-Ji Han
Eun-Young Choi
Su-Ji Jeon
Sang-Woo Lee
Jun-Mo Moon
Soo-Hyun Jung
Ji-Youn Jung
author_sort Eun-Ji Han
collection DOAJ
description Currently, therapies for treating oral cancer have various side effects; therefore, research on treatment methods employing natural substances is being conducted. This study aimed to investigate piperine-induced apoptosis and autophagy in HSC-3 human oral cancer cells and their effects on tumor growth in vivo. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that piperine reduced the viability of HSC-3 cells and 4′,6-diamidino-2-phenylindole staining, annexin-V/propidium iodide staining, and analysis of apoptosis-related protein expression confirmed that piperine induces apoptosis in HSC-3 cells. Additionally, piperine-induced autophagy was confirmed by the observation of increased acidic vesicular organelles and autophagy marker proteins, demonstrating that autophagy in HSC-3 cells induces apoptosis. Mechanistically, piperine induced apoptosis and autophagy by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in HSC-3 cells. We also confirmed that piperine inhibits oral cancer tumor growth in vivo via antitumor effects related to apoptosis and PI3K signaling pathway inhibition. Therefore, we suggest that piperine can be considered a natural anticancer agent for human oral cancer.
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spelling doaj.art-2eadcd5c95904d4aad60f07715ead9272023-11-19T11:05:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181394910.3390/ijms241813949Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling PathwayEun-Ji Han0Eun-Young Choi1Su-Ji Jeon2Sang-Woo Lee3Jun-Mo Moon4Soo-Hyun Jung5Ji-Youn Jung6Laboratory Animal Science, Department of Companion, Kongju National University, Yesan-gun 32439, Republic of KoreaLaboratory Animal Science, Department of Companion, Kongju National University, Yesan-gun 32439, Republic of KoreaLaboratory Animal Science, Department of Companion, Kongju National University, Yesan-gun 32439, Republic of KoreaLaboratory Animal Science, Department of Companion, Kongju National University, Yesan-gun 32439, Republic of KoreaLaboratory Animal Science, Department of Companion, Kongju National University, Yesan-gun 32439, Republic of KoreaLaboratory Animal Science, Department of Companion, Kongju National University, Yesan-gun 32439, Republic of KoreaLaboratory Animal Science, Department of Companion, Kongju National University, Yesan-gun 32439, Republic of KoreaCurrently, therapies for treating oral cancer have various side effects; therefore, research on treatment methods employing natural substances is being conducted. This study aimed to investigate piperine-induced apoptosis and autophagy in HSC-3 human oral cancer cells and their effects on tumor growth in vivo. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay demonstrated that piperine reduced the viability of HSC-3 cells and 4′,6-diamidino-2-phenylindole staining, annexin-V/propidium iodide staining, and analysis of apoptosis-related protein expression confirmed that piperine induces apoptosis in HSC-3 cells. Additionally, piperine-induced autophagy was confirmed by the observation of increased acidic vesicular organelles and autophagy marker proteins, demonstrating that autophagy in HSC-3 cells induces apoptosis. Mechanistically, piperine induced apoptosis and autophagy by inhibiting the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/mammalian target of rapamycin pathway in HSC-3 cells. We also confirmed that piperine inhibits oral cancer tumor growth in vivo via antitumor effects related to apoptosis and PI3K signaling pathway inhibition. Therefore, we suggest that piperine can be considered a natural anticancer agent for human oral cancer.https://www.mdpi.com/1422-0067/24/18/13949piperineapoptosisautophagyPI3K/Akt/mTOR pathwayoral canceranticancer effects
spellingShingle Eun-Ji Han
Eun-Young Choi
Su-Ji Jeon
Sang-Woo Lee
Jun-Mo Moon
Soo-Hyun Jung
Ji-Youn Jung
Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway
International Journal of Molecular Sciences
piperine
apoptosis
autophagy
PI3K/Akt/mTOR pathway
oral cancer
anticancer effects
title Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway
title_full Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway
title_fullStr Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway
title_full_unstemmed Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway
title_short Piperine Induces Apoptosis and Autophagy in HSC-3 Human Oral Cancer Cells by Regulating PI3K Signaling Pathway
title_sort piperine induces apoptosis and autophagy in hsc 3 human oral cancer cells by regulating pi3k signaling pathway
topic piperine
apoptosis
autophagy
PI3K/Akt/mTOR pathway
oral cancer
anticancer effects
url https://www.mdpi.com/1422-0067/24/18/13949
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