Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells

This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical...

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Main Authors: Linda Saxe Einbond, Jing Zhou, Kunhui Huang, Mario R. Castellanos, Emeka Mbazor, Michael Balick, Hongbao Ma, James A. DeVoti, Stephen Redenti, Hsan-au Wu
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/1/55
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author Linda Saxe Einbond
Jing Zhou
Kunhui Huang
Mario R. Castellanos
Emeka Mbazor
Michael Balick
Hongbao Ma
James A. DeVoti
Stephen Redenti
Hsan-au Wu
author_facet Linda Saxe Einbond
Jing Zhou
Kunhui Huang
Mario R. Castellanos
Emeka Mbazor
Michael Balick
Hongbao Ma
James A. DeVoti
Stephen Redenti
Hsan-au Wu
author_sort Linda Saxe Einbond
collection DOAJ
description This study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays. W12 cells, derived from a cervical precancerous lesion, contain either episomal or integrated HPV16 DNA. Several compounds, including digoxin, tanshinone IIA, dihydromethysticin and carrageenan, as well as fractions of turmeric, ginger and pomegranate inhibited the growth of W12 precancer and cervical cancer cells. Curcumin and tanshinone IIA were the most active and relatively nontoxic compounds. RT-PCR analysis showed that tanshinone IIA activated the expression of p53, while repressing the expression of HPV16 E1, E2, E4, E6, and E7 viral transcripts in W12 (type 1 and 2) integrant cells. In addition, curcumin synergized with tanshinone IIA in HeLa cells. Molecular docking studies suggested tanshinone IIA and curcumin bind to the Na<sup>+</sup>/K<sup>+</sup>-ATPase ion channel, with curcumin binding with higher affinity. Our findings highlight the potential of these multifaceted phytochemicals to prevent and treat HPV-induced cervical cancer, offering a promising approach for combinatorial therapeutic intervention.
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spelling doaj-art-e61010965c96409fb5c626eecfa698e12025-01-24T13:52:25ZengMDPI AGViruses1999-49152024-12-011715510.3390/v17010055Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer CellsLinda Saxe Einbond0Jing Zhou1Kunhui Huang2Mario R. Castellanos3Emeka Mbazor4Michael Balick5Hongbao Ma6James A. DeVoti7Stephen Redenti8Hsan-au Wu9Center for Plants, People and Culture, The New York Botanical Garden, New York, NY 10458, USALehman College and the Graduate Center, City University of New York, New York, NY 10468, USALehman College and the Graduate Center, City University of New York, New York, NY 10468, USAStaten Island University Hospital, Northwell Health, New York, NY 10305, USALehman College and the Graduate Center, City University of New York, New York, NY 10468, USACenter for Plants, People and Culture, The New York Botanical Garden, New York, NY 10458, USADepartment of Rehabilitation and Regenerative Medicine, College of Physicians and Surgeons, Columbia University, HHSC-1518, 701 W. 168th Street, New York, NY 10032, USAThe Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY 11030, USALehman College and the Graduate Center, City University of New York, New York, NY 10468, USADepartment of Rehabilitation and Regenerative Medicine, College of Physicians and Surgeons, Columbia University, HHSC-1518, 701 W. 168th Street, New York, NY 10032, USAThis study explores the effects of plant compounds on human papillomavirus (HPV)-induced W12 cervical precancer cells and bioelectric signaling. The aim is to identify effective phytochemicals, both individually and in combination, that can prevent and treat HPV infection and HPV associated cervical cancer. Phytochemicals were tested using growth inhibition, combination, gene expression, RT PCR, and molecular docking assays. W12 cells, derived from a cervical precancerous lesion, contain either episomal or integrated HPV16 DNA. Several compounds, including digoxin, tanshinone IIA, dihydromethysticin and carrageenan, as well as fractions of turmeric, ginger and pomegranate inhibited the growth of W12 precancer and cervical cancer cells. Curcumin and tanshinone IIA were the most active and relatively nontoxic compounds. RT-PCR analysis showed that tanshinone IIA activated the expression of p53, while repressing the expression of HPV16 E1, E2, E4, E6, and E7 viral transcripts in W12 (type 1 and 2) integrant cells. In addition, curcumin synergized with tanshinone IIA in HeLa cells. Molecular docking studies suggested tanshinone IIA and curcumin bind to the Na<sup>+</sup>/K<sup>+</sup>-ATPase ion channel, with curcumin binding with higher affinity. Our findings highlight the potential of these multifaceted phytochemicals to prevent and treat HPV-induced cervical cancer, offering a promising approach for combinatorial therapeutic intervention.https://www.mdpi.com/1999-4915/17/1/55bioelectricitycurcuminepisomalprecancertanshinone IIAmolecular docking
spellingShingle Linda Saxe Einbond
Jing Zhou
Kunhui Huang
Mario R. Castellanos
Emeka Mbazor
Michael Balick
Hongbao Ma
James A. DeVoti
Stephen Redenti
Hsan-au Wu
Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells
Viruses
bioelectricity
curcumin
episomal
precancer
tanshinone IIA
molecular docking
title Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells
title_full Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells
title_fullStr Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells
title_full_unstemmed Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells
title_short Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA; Tanshinone IIA Synergizes with Curcumin in Cervical Cancer Cells
title_sort plant compounds inhibit the growth of w12 cervical precancer cells containing episomal or integrant hpv dna tanshinone iia synergizes with curcumin in cervical cancer cells
topic bioelectricity
curcumin
episomal
precancer
tanshinone IIA
molecular docking
url https://www.mdpi.com/1999-4915/17/1/55
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