Bavachinin Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Small Cell Lung Cancer and Shows an Antitumor Effect in the Xenograft Model

被引：21

作者：

Hung, Shih-Ya ^{[1
,2
]}

Lin, Shih-Chao ^{[3
]}

Wang, Shuzhen ^{[4
]}

Chang, Tzu-Jung ^{[5
]}

Tung, Yu-Tang ^{[7
]}

Lin, Chi-Chien ^{[5
,8
,9
]}

Ho, Chi-Tang ^{[6
]}

Li, Shiming ^{[4
]}

机构：

[1] China Med Univ Hosp, Div Colorectal Surg, Taichung 404, Taiwan

[2] China Med Univ, Grad Inst Acupuncture Sci, Taichung 404, Taiwan

[3] Natl Taiwan Ocean Univ, Coll Life Sci, Bachelor Degree Program Marine Biotechnol, Keelung 202, Taiwan

[4] Huanggang Normal Univ, Hubei Key Lab Econ Forest Germplasm Improvement &, Huanggang 438000, Hubei, Peoples R China

[5] Natl Chung Hsing Univ, iEGG & Anim Biotechnol Ctr, Inst Biomed Sci, Taichung 402, Taiwan

[6] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA

[7] Natl Chung Hsing Univ, Grad Inst Biotechnol, Taichung 402, Taiwan

[8] China Med Univ Hosp, Dept Med Res, Taichung 404, Taiwan

[9] Kaohsiung Med Univ, Coll Med, Dept Pharmacol, Kaohsiung 807, Taiwan

来源：

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY | 2021年 / 69卷 / 22期

关键词：

small cell lung cancer; bavachinin; G2/M cell cycle arrest; apoptosis; ATM/ATR-CHK2/CHK1 signaling pathway;

D O I：

10.1021/acs.jafc.1c01657

中图分类号：

S [农业科学];

学科分类号：

09 ;

摘要：

Lung cancer is grouped into small cell lung cancer (SCLC) and non-SCLC (NSCLC). SCLC exhibits a poor prognosis, and the current anticancer treatment remains unsatisfactory. Bavachinin, present in the seed of Psoralea corylifolia, shows anti-inflammatory effects, immune modulation, and anticancer potency. This study aims to investigate the antitumor effect of bavachinin on SCLC and its underlying mechanism. The SCLC cell line H1688 was treated with different concentrations of bavachinin and showed decreased viability with arrested G2/M and sub-G1 phase cell accumulation at a concentration as low as 25 mu M. Expression levels of caspase-3, -8, and -9, as well as Fas, FasL, and Bax, increased with the concentration of bavachinin. The accumulated sub-GI cells and annexin V confirmed increasing apoptotic cancer cells after treatment. The accumulated G2/M phase cells with increasing levels of phosphorylated CDC25C, CDC2, ATM/ATR, and CHK2/CHK1 confirmed the arrested cell cycle caused by bavachinin via a dose-dependent manner. This phenomenon can be reversed by an ATM/ATR inhibitor, caffeine. Following the administration of bavachinin to xenograft mice with SCLC, the tumor burden decreased without impairing hematologic or hepatorenal functions. Bavachinin induces SCLC apoptosis via intrinsic and extrinsic pathways and causes cancer cell cycle arrest via the ATM/ATR signaling pathway.

引用

页码：6260 / 6270

页数：11

共 32 条

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