从二维到三维体外世界：C-小檗碱纳米复合物对癌细胞的声动力诱导促氧化促凋亡作用

From 2D to 3D In Vitro World: Sonodynamically-Induced Prooxidant Proapoptotic Effects of C-Berberine Nanocomplex on Cancer Cells.

作者信息

Radivoievych Aleksandar, Schnepel Sophia, Prylutska Svitlana, Ritter Uwe, Zolk Oliver, Frohme Marcus, Grebinyk Anna

机构信息

Division Molecular Biotechnology and Functional Genomics, Technical University of Applied Sciences Wildau, Hochschulring 1, 15745 Wildau, Germany.

Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, the Brandenburg Medical School Theodor Fontane and the University of Potsdam, 14476 Potsdam, Germany.

出版信息

Cancers (Basel). 2024 Sep 18;16(18):3184. doi: 10.3390/cancers16183184.

DOI:10.3390/cancers16183184

PMID:39335156

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11430052/

Abstract

OBJECTIVES

The primary objective of this research targeted the biochemical effects of SDT on human cervix carcinoma (HeLa) and mouse Lewis lung carcinoma (LLC) cells grown in 2D monolayer and 3D spheroid cell culture.

METHODS

HeLa and LLC monolayers and spheroids were treated with a 20 µM C-Ber for 24 h, followed by irradiation with 1 MHz, 1 W/cm US. To evaluate the efficacy of the proposed treatment on cancer cells, assessments of cell viability, caspase 3/7 activity, ATP levels, and ROS levels were conducted.

RESULTS

Our results revealed that US irradiation alone had negligible effects on LLC and HeLa cancer cells. However, both monolayers and spheroids irradiated with US in the presence of the C-Ber exhibited a significant decrease in viability (32% and 37%) and ATP levels (42% and 64%), along with a notable increase in ROS levels (398% and 396%) and caspase 3/7 activity (437% and 246%), for HeLa monolayers and spheroids, respectively. Similar tendencies were observed with LLC cells. In addition, the anticancer effects of C-Ber surpassed those of C, Ber, or their mixture (C + Ber) in both cell lines.

CONCLUSIONS

The detected intensified ROS generation and ATP level drop point to mitochondria dysfunction, while increased caspase 3/7 activity points on the apoptotic pathway induction. The combination of 1 W/cm US with C-Ber showcased a promising platform for synergistic sonodynamic chemotherapy for cancer treatment.

摘要

目的

本研究的主要目标是针对声动力疗法（SDT）对在二维单层和三维球体细胞培养中生长的人宫颈癌（HeLa）和小鼠Lewis肺癌（LLC）细胞的生化作用。

方法

用20μM的C-Ber处理HeLa和LLC单层细胞及球体细胞24小时，随后用1MHz、1W/cm的超声进行照射。为评估所提出的治疗方法对癌细胞的疗效，进行了细胞活力、半胱天冬酶3/7活性、ATP水平和活性氧水平的评估。

结果

我们的结果显示，单独的超声照射对LLC和HeLa癌细胞的影响可忽略不计。然而，在C-Ber存在的情况下用超声照射的单层细胞和球体细胞，HeLa单层细胞和球体细胞的活力（分别为32%和37%）和ATP水平（分别为42%和64%）均显著降低，同时活性氧水平（分别为398%和396%）和半胱天冬酶3/7活性（分别为437%和246%）显著增加。LLC细胞也观察到类似趋势。此外，在两种细胞系中，C-Ber的抗癌作用均超过了C、Ber或它们的混合物（C + Ber）。