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发酵毕赤酵母通过过度表达BAX和CASP 9基因引发人口腔鳞状细胞癌的凋亡。

Pichia fermentans originates apoptosis in human oral squamous cell carcinoma by over-expressing BAX and CASP 9 genes.

作者信息

Shamloo Hasan Bagherpour, Shahabi Arman, Aghazadeh Zahra, Yari Khosroushahi Ahmad

机构信息

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

Molecular Medicine Department, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Cytotechnology. 2020 Jun;72(3):445-454. doi: 10.1007/s10616-020-00392-w. Epub 2020 Apr 6.

Abstract

Squamous cell carcinoma (SCC) is one of the most common malignant tumors of the oral cavity. Probiotics have often been considered as effective anti-tumoral candidates. This study aimed to investigate the role of Pichia fermentans YSH secretion metabolites on the induction of apoptosis in SCC. Cytotoxicity, apoptotic effects, and visualization DNA damage were evaluated by MTT, flow cytometry, and DAPI staining assays, respectively. Real-time PCR was employed for evaluation of the mechanism of cellular apoptosis. P. fermentans YSH secretions (IC) showed cellular cytotoxicity in human tongue squamous carcinoma (HSC4, RRID:CVCL_1289) cells (85% apoptosis) similar to the cytotoxicity of cisplatin whereas only 21% apoptosis was observed in human epithelial normal (KDR, RRID:CVCL_9V14) cells. The prophylactic efficacy of reference yeast, which regarded as a reference, was not comparable to P. fermentans YSH illustrating strain-dependent properties of bioactivities on oral disease control and prevention. According to our result, the main cytotoxicity is related to apoptosis mechanisms induced by apoptosis genes inducing BAX and CASP. However, follow-up researches should be performed to recognize the compounds to be utilized as effective anticancer therapeutics.

摘要

鳞状细胞癌(SCC)是口腔最常见的恶性肿瘤之一。益生菌常被视为有效的抗肿瘤候选物。本研究旨在探讨发酵毕赤酵母YSH分泌代谢产物在诱导SCC细胞凋亡中的作用。分别通过MTT、流式细胞术和DAPI染色试验评估细胞毒性、凋亡效应和DNA损伤可视化情况。采用实时定量PCR评估细胞凋亡机制。发酵毕赤酵母YSH分泌物(IC)对人舌鳞状细胞癌(HSC4,RRID:CVCL_1289)细胞显示出细胞毒性(85%凋亡),类似于顺铂的细胞毒性,而在人正常上皮细胞(KDR,RRID:CVCL_9V14)中仅观察到21%的凋亡。作为对照的参考酵母的预防效果与发酵毕赤酵母YSH不可比,这说明了生物活性在口腔疾病控制和预防方面的菌株依赖性特性。根据我们的结果,主要细胞毒性与由诱导BAX和CASP的凋亡基因诱导的凋亡机制有关。然而,应开展后续研究以确定可作为有效抗癌治疗药物的化合物。

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