The Phytochemical α-Mangostin Inhibits Cervical Cancer Cell Proliferation and Tumor Growth by Downregulating E6/E7-HPV Oncogenes and KCNH1 Gene Expression

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.

Development of a Pseudocellular System to Quantify Specific Interactions Determining the G-Quadruplex Function in Cells

“…G-quadruplexes in template DNAs have been reported to inhibit gene transcription or damage sequences, depending on their stability (Figure a). ,− Thus, we sought to confirm whether SHELL would recapitulate these of G-quadruplex stability on transcription.…”

“…G-quadruplex in MCF-7 showed a smaller −Δ n K + value, indicating that changes in G-quadruplex stability with fluctuating K + are less than those in MDA-MD-231. We previously demonstrated that the transcription efficiency (TE) of an oncogene harboring a G-quadruplex in MCF-7 cells was lower than that in MDA-MD-231 cells owing to perturbations in K + concentration caused by KCNH1 overexpression. , The changes in TE values indicate that the G-quadruplex is more susceptible to destabilization in MDA-MD-231 cells than in MCF-7 cells, likely because of differences in cation-G-quadruplex binding resulting from the distinct molecular environments in each cell. This phenomenon was consistent with the SHELL results.…”

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“…The antiviral activity of alpha-mangostin has been investigated against a wide range of viruses, including both DNA and RNA viruses. Numerous in vitro and in vivo studies have provided valuable insights into its efficacy against various viral infections [13,14,21,23]. The following subsections highlight the antiviral activity of alpha-mangostin against different viral families:…”

“…Safety considerations and potential toxicity profiles also require comprehensive evaluation. In addition, the synergistic effects of alpha-mangostin in combination with other antiviral agents should be investigated to enhance its therapeutic potential [13][14][15]. In this mini review, we aim to provide an overview of the current literature on alpha-mangostin as an antiviral candidate.…”

The Preventive Role of the Vitamin D Endocrine System in Cervical Cancer

“…Interestingly, despite having a high HPV16 number of copies, CaSki cells are very sensitive to the effects of antiproliferative factors. Recently, we have demonstrated that the natural compound α-mangostin inhibited the proliferation of CaSki cells, a process that was accompanied by the reduction in the expression of EAG1 and HPV16 E6/E7 oncogenes [70].…”