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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1797579715013246976 |
---|---|
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. |
first_indexed | 2024-03-10T22:40:04Z |
format | Article |
id | doaj.art-2eadcd5c95904d4aad60f07715ead927 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T22:40:04Z |
publishDate | 2023-09-01 |
publisher | MDPI AG |
record_format | Article |
series | International Journal of Molecular Sciences |
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 |
work_keys_str_mv | AT eunjihan piperineinducesapoptosisandautophagyinhsc3humanoralcancercellsbyregulatingpi3ksignalingpathway AT eunyoungchoi piperineinducesapoptosisandautophagyinhsc3humanoralcancercellsbyregulatingpi3ksignalingpathway AT sujijeon piperineinducesapoptosisandautophagyinhsc3humanoralcancercellsbyregulatingpi3ksignalingpathway AT sangwoolee piperineinducesapoptosisandautophagyinhsc3humanoralcancercellsbyregulatingpi3ksignalingpathway AT junmomoon piperineinducesapoptosisandautophagyinhsc3humanoralcancercellsbyregulatingpi3ksignalingpathway AT soohyunjung piperineinducesapoptosisandautophagyinhsc3humanoralcancercellsbyregulatingpi3ksignalingpathway AT jiyounjung piperineinducesapoptosisandautophagyinhsc3humanoralcancercellsbyregulatingpi3ksignalingpathway |