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Plant Compounds Inhibit the Growth of W12 Cervical Precancer Cells Containing Episomal or Integrant HPV DNA;
Linda Saxe Einbond1,2,3, Jing Zhou2, Kunhui Huang2
1Center for Plants, People and Culture, The New York Botanical Garden, New York, NY 10458, USA.
Abstract:
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+/K+-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.
Insights
Plant compounds like curcumin and tanshinone IIA show promise in preventing and treating human papillomavirus (HPV)-induced cervical cancer by inhibiting precancer cell growth and targeting viral gene expression.
Area of Science:
- Phytochemistry
- Oncology
- Virology
- Molecular Biology
Background:
- Human papillomavirus (HPV) is a major cause of cervical cancer.
- Cervical precancerous lesions (W12 cells) provide a model for studying HPV-associated cancer development.
- Identifying novel therapeutic agents for HPV-induced cervical cancer is crucial.
Purpose of the Study:
- To investigate the effects of various plant compounds (phytochemicals) on HPV-induced cervical precancer cells.
- To identify effective phytochemicals, individually and in combination, for preventing and treating HPV infection and cervical cancer.
- To explore the molecular mechanisms underlying the action of these compounds.
Main Methods:
- Growth inhibition assays
- Combination assays
- Gene expression analysis (RT-PCR)
- Molecular docking studies
- Utilized W12 cervical precancer cells and HeLa cells.
Main Results:
- Several phytochemicals, including tanshinone IIA and curcumin, inhibited W12 precancer and cervical cancer cell growth.
- Tanshinone IIA activated p53 expression and repressed HPV16 viral transcripts (E1, E2, E4, E6, E7).
- Curcumin and tanshinone IIA demonstrated synergistic effects in HeLa cells and potential binding to the Na+/K+-ATPase ion channel.
Conclusions:
- Phytochemicals like curcumin and tanshinone IIA hold significant potential for preventing and treating HPV-induced cervical cancer.
- Combinatorial therapeutic strategies using these compounds offer a promising approach.
- Targeting bioelectric signaling and viral gene expression are key mechanisms of action.
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