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木豆叶提取物对人宫颈癌 Hela 细胞的细胞毒性作用及诱导凋亡的研究

Cytotoxic effect and induction of apoptosis in human cervical cancer cells by a wood extract from .

机构信息

Centro Interdisciplinario de Investigación para el Desarrollo Integral Regional - Unidad Durango, Instituto Politécnico Nacional, Durango, Dgo, México.

Facultad de Química, Universidad Nacional Autónoma de México, Alc. Coyoacán, Ciudad de México, México.

出版信息

Drug Chem Toxicol. 2023 Nov;46(5):931-943. doi: 10.1080/01480545.2022.2109046. Epub 2022 Aug 11.

DOI:10.1080/01480545.2022.2109046
PMID:35950554
Abstract

Cervical cancer ranks fourth in incidence among women worldwide. Cisplatin is currently the first-line drug of treatment for cervical cancer; however, it causes serious adverse effects. Therefore, it is crucial to explore natural products for cervical cancer treatment. is a medicinal plant frequently used for ophthalmological and gastrointestinal infections. In this study, we used the MTT cell viability assay to evaluate the cytotoxic effect of a wood extract from (Extract T7) in SiHa, HeLa, Ca Ski, and C-33 A cancer cell lines. Phosphatidylserine translocation and cell cycle evaluations were performed to determine the mechanism of cellular death. The extract's safety was evaluated using the Ames test with strains, acute toxicity assay, and repeated dose toxicity assay in mice. We also identified phenolic compounds of Extract T7 through liquid chromatography/mass spectrometry. Naringin, catechin, and eriodictyol demonstrated a higher concentration in Extract T7. Additionally, Extract T7 exhibited a cytotoxic effect against cervical cancer cells, where C-33 A was the most sensitive (IC= 22.58 ± 1.10 µg/mL and 14.26 ± 1.11 µg/mL at 24 h and 48 h respectively). Extract T7 induced death by apoptosis and cell cycle arrest in the G phase in C-33 A. Extract T7 was not mutagenic. No toxicological effects were observed during acute toxicity and repeated dose toxicity for 28 days. Therefore, further evaluations of Extract T7 should be conducted to identify the complete mechanism of action for potential anti-tumoral activity and safety before conducting studies in animal models.

摘要

宫颈癌在全球女性中发病率居第四位。顺铂是目前治疗宫颈癌的一线药物;然而,它会引起严重的不良反应。因此,探索治疗宫颈癌的天然产物至关重要。 是一种药用植物,常用于治疗眼科和胃肠道感染。在本研究中,我们使用 MTT 细胞活力测定法评估了 (Extract T7)木材提取物对 SiHa、HeLa、Ca Ski 和 C-33 A 癌细胞系的细胞毒性作用。通过磷脂酰丝氨酸易位和细胞周期评估来确定细胞死亡的机制。使用 Ames 试验对 5 株菌株、急性毒性试验和小鼠重复剂量毒性试验评估提取物的安全性。我们还通过液相色谱/质谱法鉴定了 Extract T7 中的酚类化合物。柚皮苷、儿茶素和圣草酚在 Extract T7 中的浓度较高。此外,Extract T7 对宫颈癌细胞具有细胞毒性作用,其中 C-33 A 最为敏感(24 h 和 48 h 时 IC=22.58±1.10 µg/mL 和 14.26±1.11 µg/mL)。Extract T7 通过诱导细胞凋亡和 C-33 A 细胞周期阻滞在 G 期导致细胞死亡。Extract T7 无致突变性。在急性毒性和重复剂量毒性试验 28 天内未观察到毒性作用。因此,在进行动物模型研究之前,应对 Extract T7 进行进一步评估,以确定其潜在抗肿瘤活性和安全性的完整作用机制。

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