Departamento de Biología de la Reproducción Dr. Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico.
Departamento de Biología Molecular y Biotecnología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Int J Mol Sci. 2023 Feb 3;24(3):3055. doi: 10.3390/ijms24033055.
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 . The phytochemical α-mangostin (AM) is a potent antineoplastic and antiviral compound. However, its effects on HPV oncogenes and 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 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.
宫颈癌是全球女性中第四常见的癌症。这种肿瘤的发生和进展的主要因素是人类乳头瘤病毒（HPV）感染。HPV 癌基因 E6 和 E7 是细胞转化的关键驱动因素，促进了 等癌基因的表达。植物化学物质 α-倒捻子素（AM）是一种有效的抗肿瘤和抗病毒化合物。然而，其对 HPV 癌基因和 基因表达的影响尚不清楚。本研究评估了 AM 对细胞增殖、细胞周期分布和基因表达的影响，包括其对异种移植小鼠肿瘤生长的影响。AM 呈浓度依赖性抑制细胞增殖，对 HPV16 拷贝数最高的细胞系最为敏感。此外，AM 促进了 CaSki 细胞的 G1 细胞周期停滞，而在 SiHa 和 HeLa 细胞中则导致细胞死亡。有趣的是，我们发现 AM 依赖性地降低了 E6、E7 和 在体外和体内的基因表达，以及细胞因子表达、Ki-67 和肿瘤生长抑制的调节。基于这些发现，我们认为 AM 是治疗和预防宫颈癌的一种很好的辅助药物选择。
