The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo

Zohreh Salari; Ahmad Khosravi; Elham Pourkhandani; Elaheh Molaakbari; Ehsan Salarkia; Alireza Keyhani; Iraj Sharifi; Hadi Tavakkoli; Samira Sohbati; Shahriar Dabiri; Guogang Ren; Mohammad Shafie’ei

doi:10.3389/fonc.2023.1098429

The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo

Zohreh Salari, Ahmad Khosravi, Elham Pourkhandani, Elaheh Molaakbari, Ehsan Salarkia, Alireza Keyhani, Iraj Sharifi, Hadi Tavakkoli, Samira Sohbati, Shahriar Dabiri, Guogang Ren, Mohammad Shafie’ei

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Abstract

Background: Epithelial ovarian cancer is very common in women and causes hundreds of deaths per year worldwide. Chemotherapy drugs including cisplatin have adverse effects on patients’ health. Complementary treatments and the use of herbal medicines can help improve the performance of medicine. 6-Gingerol is the major pharmacologically active component of ginger. In this study, we compared the effects of 6-gingerol, cisplatin, and their combination in apoptotic and angiogenetic activities in silico, in test tubes, and in in vivo assays against two ovarian cancer cell lines: OVCAR-3 and human umbilical vein endothelial cells (HUVECs). Methods: The drug-treated cell lines were evaluated for their cytotoxicity, cell cycle, and apoptotic and angiogenetic gene expression changes.

Results: The proportion of apoptosis treated by 6-gingerol coupled with cisplatin was significantly high. In the evaluation of the cell cycle, the combination therapy also showed a significant promotion of a higher extent of the S sequence. The expression of p53 level, Caspase-8, Bax, and Apaf1 genes was amplified again with combination therapy. Conversely, in both cell lines, the cumulative drug concentrations reduced the expression of VEGF, FLT1, KDR, and Bcl-2 genes. Similarly, in the control group, combination treatment significantly decreased the expression of VEGF, FLT1, KDR, and Bcl-2 genes in comparison to cisplatin alone.

Conclusions: The findings of the present study demonstrated that the cisplatin and 6-gingerol combination is more effective in inducing apoptosis and suppressing the angiogenesis of ovarian cancer cells than using each drug alone.

Original language	English
Article number	1098429
Pages (from-to)	1-17
Number of pages	17
Journal	Frontiers in Oncology
Volume	13
Early online date	3 Mar 2023
DOIs	https://doi.org/10.3389/fonc.2023.1098429
Publication status	Published - 3 Mar 2023

Keywords

Oncology
ovarian neoplasm
gingerol
cisplatin
apoptosis
angiogenesis
molecular dynamics simulation
chick embryo

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10.3389/fonc.2023.1098429Licence: CC BY

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© 2023 Salari, Khosravi, Pourkhandani, Molaakbari, Salarkia, Keyhani, Sharifi, Tavakkoli, Sohbati, Dabiri, Ren and Shafie’ei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/
Final published version, 12.2 MBLicence: CC BY

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Salari, Z., Khosravi, A., Pourkhandani, E., Molaakbari, E., Salarkia, E., Keyhani, A., Sharifi, I., Tavakkoli, H., Sohbati, S., Dabiri, S., Ren, G., & Shafie’ei, M. (2023). The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo. Frontiers in Oncology, 13, 1-17. Article 1098429. https://doi.org/10.3389/fonc.2023.1098429

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title = "The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo",

abstract = "Background: Epithelial ovarian cancer is very common in women and causes hundreds of deaths per year worldwide. Chemotherapy drugs including cisplatin have adverse effects on patients{\textquoteright} health. Complementary treatments and the use of herbal medicines can help improve the performance of medicine. 6-Gingerol is the major pharmacologically active component of ginger. In this study, we compared the effects of 6-gingerol, cisplatin, and their combination in apoptotic and angiogenetic activities in silico, in test tubes, and in in vivo assays against two ovarian cancer cell lines: OVCAR-3 and human umbilical vein endothelial cells (HUVECs). Methods: The drug-treated cell lines were evaluated for their cytotoxicity, cell cycle, and apoptotic and angiogenetic gene expression changes. Results: The proportion of apoptosis treated by 6-gingerol coupled with cisplatin was significantly high. In the evaluation of the cell cycle, the combination therapy also showed a significant promotion of a higher extent of the S sequence. The expression of p53 level, Caspase-8, Bax, and Apaf1 genes was amplified again with combination therapy. Conversely, in both cell lines, the cumulative drug concentrations reduced the expression of VEGF, FLT1, KDR, and Bcl-2 genes. Similarly, in the control group, combination treatment significantly decreased the expression of VEGF, FLT1, KDR, and Bcl-2 genes in comparison to cisplatin alone. Conclusions: The findings of the present study demonstrated that the cisplatin and 6-gingerol combination is more effective in inducing apoptosis and suppressing the angiogenesis of ovarian cancer cells than using each drug alone.",

keywords = "Oncology, ovarian neoplasm, gingerol, cisplatin, apoptosis, angiogenesis, molecular dynamics simulation, chick embryo",

author = "Zohreh Salari and Ahmad Khosravi and Elham Pourkhandani and Elaheh Molaakbari and Ehsan Salarkia and Alireza Keyhani and Iraj Sharifi and Hadi Tavakkoli and Samira Sohbati and Shahriar Dabiri and Guogang Ren and Mohammad Shafie{\textquoteright}ei",

note = " {\textcopyright} 2023 Salari, Khosravi, Pourkhandani, Molaakbari, Salarkia, Keyhani, Sharifi, Tavakkoli, Sohbati, Dabiri, Ren and Shafie{\textquoteright}ei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/",

year = "2023",

month = mar,

day = "3",

doi = "10.3389/fonc.2023.1098429",

language = "English",

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Salari, Z, Khosravi, A, Pourkhandani, E, Molaakbari, E, Salarkia, E, Keyhani, A, Sharifi, I, Tavakkoli, H, Sohbati, S, Dabiri, S, Ren, G & Shafie’ei, M 2023, 'The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo', Frontiers in Oncology, vol. 13, 1098429, pp. 1-17. https://doi.org/10.3389/fonc.2023.1098429

TY - JOUR

T1 - The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo

AU - Salari, Zohreh

AU - Khosravi, Ahmad

AU - Pourkhandani, Elham

AU - Molaakbari, Elaheh

AU - Salarkia, Ehsan

AU - Keyhani, Alireza

AU - Sharifi, Iraj

AU - Tavakkoli, Hadi

AU - Sohbati, Samira

AU - Dabiri, Shahriar

AU - Ren, Guogang

AU - Shafie’ei, Mohammad

N1 - © 2023 Salari, Khosravi, Pourkhandani, Molaakbari, Salarkia, Keyhani, Sharifi, Tavakkoli, Sohbati, Dabiri, Ren and Shafie’ei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/

PY - 2023/3/3

Y1 - 2023/3/3

N2 - Background: Epithelial ovarian cancer is very common in women and causes hundreds of deaths per year worldwide. Chemotherapy drugs including cisplatin have adverse effects on patients’ health. Complementary treatments and the use of herbal medicines can help improve the performance of medicine. 6-Gingerol is the major pharmacologically active component of ginger. In this study, we compared the effects of 6-gingerol, cisplatin, and their combination in apoptotic and angiogenetic activities in silico, in test tubes, and in in vivo assays against two ovarian cancer cell lines: OVCAR-3 and human umbilical vein endothelial cells (HUVECs). Methods: The drug-treated cell lines were evaluated for their cytotoxicity, cell cycle, and apoptotic and angiogenetic gene expression changes. Results: The proportion of apoptosis treated by 6-gingerol coupled with cisplatin was significantly high. In the evaluation of the cell cycle, the combination therapy also showed a significant promotion of a higher extent of the S sequence. The expression of p53 level, Caspase-8, Bax, and Apaf1 genes was amplified again with combination therapy. Conversely, in both cell lines, the cumulative drug concentrations reduced the expression of VEGF, FLT1, KDR, and Bcl-2 genes. Similarly, in the control group, combination treatment significantly decreased the expression of VEGF, FLT1, KDR, and Bcl-2 genes in comparison to cisplatin alone. Conclusions: The findings of the present study demonstrated that the cisplatin and 6-gingerol combination is more effective in inducing apoptosis and suppressing the angiogenesis of ovarian cancer cells than using each drug alone.

AB - Background: Epithelial ovarian cancer is very common in women and causes hundreds of deaths per year worldwide. Chemotherapy drugs including cisplatin have adverse effects on patients’ health. Complementary treatments and the use of herbal medicines can help improve the performance of medicine. 6-Gingerol is the major pharmacologically active component of ginger. In this study, we compared the effects of 6-gingerol, cisplatin, and their combination in apoptotic and angiogenetic activities in silico, in test tubes, and in in vivo assays against two ovarian cancer cell lines: OVCAR-3 and human umbilical vein endothelial cells (HUVECs). Methods: The drug-treated cell lines were evaluated for their cytotoxicity, cell cycle, and apoptotic and angiogenetic gene expression changes. Results: The proportion of apoptosis treated by 6-gingerol coupled with cisplatin was significantly high. In the evaluation of the cell cycle, the combination therapy also showed a significant promotion of a higher extent of the S sequence. The expression of p53 level, Caspase-8, Bax, and Apaf1 genes was amplified again with combination therapy. Conversely, in both cell lines, the cumulative drug concentrations reduced the expression of VEGF, FLT1, KDR, and Bcl-2 genes. Similarly, in the control group, combination treatment significantly decreased the expression of VEGF, FLT1, KDR, and Bcl-2 genes in comparison to cisplatin alone. Conclusions: The findings of the present study demonstrated that the cisplatin and 6-gingerol combination is more effective in inducing apoptosis and suppressing the angiogenesis of ovarian cancer cells than using each drug alone.

KW - Oncology

KW - ovarian neoplasm

KW - gingerol

KW - cisplatin

KW - apoptosis

KW - angiogenesis

KW - molecular dynamics simulation

KW - chick embryo

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U2 - 10.3389/fonc.2023.1098429

DO - 10.3389/fonc.2023.1098429

M3 - Article

C2 - 36937441

VL - 13

SP - 1

EP - 17

JO - Frontiers in Oncology

JF - Frontiers in Oncology

M1 - 1098429

ER -

The inhibitory effect of 6-gingerol and cisplatin on ovarian cancer and antitumor activity: In silico, in vitro, and in vivo

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