School of Life Sciences, Manipal Academy of Higher Education, Dubai, UAE.
Eur Rev Med Pharmacol Sci. 2021 Mar;25(5):2206-2220. doi: 10.26355/eurrev_202103_25253.
Chrysin, one of the main active constituents of flavonoids, is known for demonstrating protective effects against various types of cancer including cervical cancer. The aim of this study was to determine apoptosis induction and antiproliferative action of chrysin on human cervical cancer cells.
In this study, attempts have been made to establish anticancer role of chrysin on HeLa cells. MTT, mitochondrial potential, DNA fragmentation, annexin V/propidium iodide assays, qPCR and protein profiling were performed.
Chrysin treated HeLa cells showed time and dose dependent decrease in cell viability and demonstrated profound effects on nuclear morphology and DNA fragmentation. Chrysin treatment increased the expression of proapoptotic genes BAD, BAX, BID, BOK and APAF1, TNF, FASL, FAS, FADD and caspases (like caspase 3, caspase 7, caspase 8 and caspase 9), whereas it decreased the expression level of antiapoptotic genes MCL-1, NAIP, XIAP and Bcl-2 and cell cycle regulatory genes CCNB1, CCNB2, CCND1, CCND2, CCND3, CCNE2, CDK4 and CDK2 at transcript level. Furthermore, chrysin significantly upregulated pro-apoptotic proteins, like TRAILR2/DR5, TRAILR1/DR4, Fas/TNFRSF6/CD95, phosphoP53(S15), BAD, BAX, cleaved caspase 3, procaspase 3, HTRA2/Omi and SMAC/Diablo, while downregulated anti-apoptotic proteins like BCL-X, BCL2, XIAP and CIAPs that support chrysin mediated apoptosis in HeLa cells. Remarkably, chrysin downregulated the phosphorylated AKT pathway proteins, (p-473) AKT, (p-Ser 2448) mTOR, (p-Ser241) PDK1, (p-Ser112) BAD, and upregulated (p-Ser21) GSK3b, (p-Thr172) AMPKa, P27 (p-Thr198) and (p-Ser15) P53, which endorses chrysin mediated apoptosis.
Chrysin significantly inhibited proliferation and induced apoptosis by modulation of various apoptotic genes and AKT/MAPK pathway genes.
白杨素是黄酮类化合物的主要活性成分之一，已知其对多种癌症（包括宫颈癌）具有保护作用。本研究旨在确定白杨素对人宫颈癌 HeLa 细胞的诱导凋亡和抗增殖作用。
本研究试图确立白杨素对 HeLa 细胞的抗癌作用。进行了 MTT、线粒体电位、DNA 片段化、 Annexin V/碘化丙啶检测、qPCR 和蛋白质谱分析。
白杨素处理的 HeLa 细胞表现出细胞活力的时间和剂量依赖性下降，并对核形态和 DNA 片段化产生显著影响。白杨素处理增加了促凋亡基因 BAD、BAX、BID、BOK 和 APAF1、TNF、FASL、FAS、FADD 和半胱天冬酶（如 caspase 3、caspase 7、caspase 8 和 caspase 9）的表达，而降低了抗凋亡基因 MCL-1、NAIP、XIAP 和 Bcl-2 以及细胞周期调节基因 CCNB1、CCNB2、CCND1、CCND2、CCND3、CCNE2、CDK4 和 CDK2 的表达水平。此外，白杨素显著上调了促凋亡蛋白，如 TRAILR2/DR5、TRAILR1/DR4、Fas/TNFRSF6/CD95、磷酸化 P53（S15）、BAD、BAX、裂解 caspase 3、原 caspase 3、HTRA2/Omi 和 SMAC/ Diablo，同时下调了抗凋亡蛋白，如 BCL-X、BCL2、XIAP 和 CIAPs，支持白杨素介导的 HeLa 细胞凋亡。值得注意的是，白杨素下调了磷酸化 AKT 通路蛋白（p-473）AKT、（p-Ser2448）mTOR、（p-Ser241）PDK1、（p-Ser112）BAD，而上调了（p-Ser21）GSK3β、（p-Thr172）AMPKa、P27（p-Thr198）和（p-Ser15）P53，这支持了白杨素介导的凋亡。
白杨素通过调节多种凋亡基因和 AKT/MAPK 通路基因，显著抑制增殖并诱导凋亡。
