Antiproliferative Activity of Gibbosic Acid H through Induction of G0/G1 Cell Cycle Arrest and Apoptosis in Human Lung Cancer Cells.

IF 2.5 Q3 ONCOLOGY Journal of Cancer Prevention Pub Date : 2023-12-30 DOI:10.15430/JCP.2023.28.4.201
Jaeho Han, Donghwa Kim, Hyen Joo Park, Hee-Juhn Park, Sang Kook Lee
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Abstract

Lung cancer is one of the most common causative cancers worldwide. Particularly, non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. NSCLC is a serious form of lung cancer that requires prompt diagnosis, and the 5-year survival rate for patients with this disease is only 24%. Gibbosic acid H (GaH), a natural lanostanoid obtained from the Ganoderma species (Ganodermataceae), has antiproliferative activities against colon and lung cancer cells. The aim of the present study was to evaluate the antiproliferative activity of GaH in NSCLC cells and to elucidate the underlying molecular mechanisms. GaH was found to induce G0/G1 cell cycle arrest and autophagy by activating adenosine monophosphate-activated protein kinase in A549 and H1299 cells. The induction of this cell cycle arrest was associated with the downregulation of cyclin E1 and CDK2. Additionally, the induction of autophagy by GaH was correlated with the upregulation of LC3B, beclin-1, and p53 expression. GaH also induced apoptosis by upregulating cleaved caspase-3 and Bax in the lung cancer cells. These findings suggest that GaH has a potential in the growth inhibition of human lung cancer cells.

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吉布斯酸 H 通过诱导 G0/G1 细胞周期停滞和凋亡对人类肺癌细胞的抗增殖活性
肺癌是全球最常见的致癌癌症之一。其中,非小细胞肺癌(NSCLC)约占肺癌病例总数的 85%。非小细胞肺癌是一种需要及时诊断的严重肺癌,该病患者的 5 年生存率仅为 24%。吉布斯酸 H(GaH)是从灵芝(灵芝科)中提取的一种天然羊齿甾类化合物,对结肠癌和肺癌细胞具有抗增殖活性。本研究旨在评估GaH在NSCLC细胞中的抗增殖活性,并阐明其潜在的分子机制。研究发现,在A549和H1299细胞中,GaH通过激活单磷酸腺苷活化蛋白激酶诱导G0/G1细胞周期停滞和自噬。这种细胞周期停滞的诱导与细胞周期蛋白 E1 和 CDK2 的下调有关。此外,GaH 诱导自噬与 LC3B、beclin-1 和 p53 表达的上调有关。GaH 还通过上调肺癌细胞中的裂解 Caspase-3 和 Bax 来诱导细胞凋亡。这些发现表明,GaH 具有抑制人类肺癌细胞生长的潜力。
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