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The Phytochemical α-Mangostin Inhibits Cervical Cancer Cell Proliferation and Tumor Growth by Downregulating E6/E7-HPV Oncogenes and KCNH1 Gene Expression.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2023 Feb 03; Vol. 24 (3). Date of Electronic Publication: 2023 Feb 03. - Publication Year :
- 2023
-
Abstract
- Cervical cancer is the fourth most common cancer among women worldwide. The main factor associated with the onset and progression of this neoplasia is the human papillomavirus (HPV) infection. The HPV-oncogenes E6 and E7 are critical drivers of cellular transformation, promoting the expression of oncogenes such as KCNH1 . The phytochemical α-mangostin (AM) is a potent antineoplastic and antiviral compound. However, its effects on HPV oncogenes and KCNH1 gene expression remain unknown. This study evaluated the effects of AM on cell proliferation, cell cycle distribution and gene expression, including its effects on tumor growth in xenografted mice. AM inhibited cell proliferation in a concentration-dependent manner, being the most sensitive cell lines those with the highest number of HPV16 copies. In addition, AM promoted G1-cell cycle arrest in CaSki cells, while led to cell death in SiHa and HeLa cells. Of interest was the finding of an AM-dependent decreased gene expression of E6, E7 and KCNH1 both in vitro and in vivo, as well as the modulation of cytokine expression, Ki-67, and tumor growth inhibition. On these bases, we suggest that AM represents a good option as an adjuvant for the treatment and prevention of cervical cancer.
- Subjects :
- Humans
Female
Animals
Mice
HeLa Cells
Papillomavirus E7 Proteins genetics
Papillomavirus E7 Proteins metabolism
Repressor Proteins genetics
Oncogenes
Cell Proliferation
Gene Expression
Ether-A-Go-Go Potassium Channels genetics
Uterine Cervical Neoplasms drug therapy
Uterine Cervical Neoplasms genetics
Uterine Cervical Neoplasms pathology
Oncogene Proteins, Viral genetics
Oncogene Proteins, Viral metabolism
Papillomavirus Infections
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 24
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 36769377
- Full Text :
- https://doi.org/10.3390/ijms24033055