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The Phytochemical α-Mangostin Inhibits Cervical Cancer Cell Proliferation and Tumor Growth by Downregulating

Lorenza Díaz1, Samantha V Bernadez-Vallejo1, Rafael Vargas-Castro1

  • 1Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico.

International Journal of Molecular Sciences
|February 11, 2023
PubMed

Insights

The phytochemical α-mangostin (AM) inhibits cervical cancer cell growth by reducing human papillomavirus (HPV) oncogenes and KCNH1 expression. AM shows potential as an adjuvant therapy for cervical cancer prevention and treatment.

Area of Science:

  • Oncology
  • Virology
  • Pharmacology

Background:

  • Cervical cancer is a major global health concern, primarily driven by human papillomavirus (HPV) infection.
  • HPV oncogenes E6 and E7 are key factors in cellular transformation, influencing genes like KCNH1.
  • The potential of the phytochemical α-mangostin (AM) as an antineoplastic and antiviral agent warrants investigation regarding its effects on HPV and KCNH1.

Purpose of the Study:

  • To investigate the effects of α-mangostin (AM) on cervical cancer cell proliferation, cell cycle, and gene expression, including HPV oncogenes and KCNH1.
  • To evaluate the efficacy of AM in inhibiting tumor growth in a xenograft mouse model.
  • To explore AM's potential as an adjuvant therapy for cervical cancer.

Main Methods:

  • In vitro assessment of AM's impact on cervical cancer cell lines (CaSki, SiHa, HeLa) regarding proliferation and cell cycle distribution.
  • Quantitative analysis of E6, E7, and KCNH1 gene expression in response to AM treatment, both in vitro and in vivo.
  • In vivo studies using xenografted mice to evaluate AM's effect on tumor growth and related biomarkers like Ki-67 and cytokine expression.

Main Results:

  • AM inhibited cervical cancer cell proliferation in a dose-dependent manner, with higher sensitivity in cell lines with more HPV16 copies.
  • AM induced G1-cell cycle arrest in CaSki cells and apoptosis in SiHa and HeLa cells.
  • AM significantly decreased the expression of HPV E6, E7, and KCNH1 genes in vitro and in vivo, modulated cytokine expression, reduced Ki-67, and inhibited tumor growth.

Conclusions:

  • α-mangostin demonstrates significant antineoplastic activity against cervical cancer cells by targeting key viral oncogenes and host factors.
  • AM effectively inhibits tumor growth and modulates relevant biomarkers, suggesting its therapeutic potential.
  • AM is a promising candidate for adjuvant therapy in the treatment and prevention of cervical cancer.
Keywords:
E6E7HPVKCNH1cervical cancerα-mangostin

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