Glaucocalyxin A induces apoptosis of non-small cell lung carcinoma cells by inhibiting the PI3K/Akt/GSK3β pathway.

Abstract

Lung cancer is one of the fastest growing malignancies in morbidity and mortality, and current therapies are in general not sufficiently effective for this deadly disease. This study characterizes the anticancer effects of glaucocalyxin A (GLA) and explores the underlying mechanisms using human non-small cell lung carcinoma (NSCLC) cells. First, our data showed that GLA suppressed the viability of cancer cells, whereas no effect was observed in the normal bronchial epithelial cell BEAS-2B cells. Second, GLA inhibited colony formation, induced apoptosis of cancer cells. Third, GLA downregulated the expression of B-cell lymphoma-2 (Bcl-2) protein; upregulated the expression of Bcl2-associated X protein (Bax), and strengthened cleavage of caspase 3 and polyadenyl diphosphate ribose polymerase (PARP). Fourth, GLA also diminished mitochondrial membrane potential and inhibited phosphatidylinositol 3-kinase (PI3K)/Akt/ glycogen synthase kinase-3β (GSK3β) pathway. In addition, injection of GLA (20 mg/kg) every 2 days significantly inhibited A549 xenograft tumour growth, accompanied by increased apoptosis and decreased proliferation. Together, our study provides evidence that the anticancer effect of GLA in NSCLC is mediated by inducing apoptosis through inhibiting PI3K/Akt/GSK3β pathway and suggests that GLA may be used as a promising natural medicine for NSCLC therapy.

• Authors: De Zhang, Ting Deng, Wa Yuan, Tongqiang Chen, Shuping Jiang
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 49 Issue 8 Pg. 797-804 (08 2022) ISSN: 1440-1681 [Electronic] Australia
• PMID: 35576104 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons Australia, Ltd.

Chemical References

• Antineoplastic Agents
• Diterpenes, Kaurane
• glaucocalyxin A
• Phosphatidylinositol 3-Kinase
• Glycogen Synthase Kinase 3 beta
• Proto-Oncogene Proteins c-akt

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Diterpenes, Kaurane (pharmacology, therapeutic use)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Humans
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Phosphatidylinositol 3-Kinase (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction