Pseudolaric acid B exerts antitumor activity via suppression of the Akt signaling pathway in HeLa cervical cancer cells

Abstract

Pseudolaric acid B (PAB) is a diterpene acid isolated from the bark of the root and trunk of Pseudolarix kaempferi Gordon (Pinaceae), which has demonstrated cytotoxic effects against various types of cancer. However, the mechanisms underlying the anticancer effects of PAB have remained to be elucidated. In the present study, the effects of PAB on the viability and apoptosis of HeLa cells were investigated by MTT assay, flow cytometric analysis of Annexin V-fluorescein isothiocyanate/propidium iodide staining, Rhodamine 123 staining and western blot analysis. The results demonstrated that PAB had antiproliferative and apoptosis-inducing effects on HeLa cells. PAB markedly inhibited HeLa cell viability in a time- and concentration-dependent manner. Flow cytometric analysis indicated that PAB induced apoptosis in HeLa cells in a dose-dependent manner. Treatment with PAB suppressed the expression of anti-apoptotic factor B cell lymphoma-2, and promoted the expression of pro-apoptotic factor Bcl-2-associated X protein. In addition, PAB induced an increase in Caspase-3 activity and loss of mitochondrial membrane potential, suggesting that this apoptosis may be mediated by mitochondrial pathways. Furthermore, the results of western blot analysis indicated that PAB was able to reduce Akt phosphorylation, thereby inhibiting the Akt pathway. These results suggested that PAB inhibited cell proliferation and induced apoptosis in HeLa cells, and that the anti-tumor effects of PAB were associated with inhibition of the Akt pathway. In conclusion, the results of the present study suggested that PAB may represent a novel therapeutic strategy for the treatment of human cervical cancer. However, additional studies are required to investigate the underlying apoptotic mechanisms.

Pseudolaric Acid B Induces Growth Inhibition and Caspase-Dependent Apoptosis on Head and Neck Cancer Cell lines through Death Receptor 5

“…However, most of findings on PAB-induced apoptosis focused on intrinsic apoptotic pathway. For examples, PAB inhibits mitochondria-mediated apoptosis pathways in human gastric carcinoma BGC-823 and MKN-45 cells and cervical cancer HeLa cells through the modification of the ratio of Bax/Bcl-2 [12,37]. PAB also induced apoptosis via proteasome-mediated protein degradation of Bcl-2 in human prostate cancer DU145 cells [38].…”

“…[7]. Among the studies, it has shown that PAB has strong cytotoxic effects on various types of cancers, including colorectal cancer, gastric cancer, liver cancer, prostate cancer, lung cancer, melanoma, and leukemia [8,9,10,11,12,13,14,15,16]. However, there has not been yet a single research on HNCs.…”

Diterpenes and Their Derivatives as Potential Anticancer Agents

“…On the other hand, the diterpenoid C from Radix curcumae in human colon adenocarcinoma SW620 cells significantly inhibited cell proliferation and induced apoptosis by MAPK signalling and caspase‐3 dependent pathways (Shen et al , ). The other antiproliferative and apoptosis‐inducing diterpenes are pseudolaric acid B (Yu et al , ), oridonin (Yang et al , ), pseudolaric acid B (Li and Hong, ), crypotanshinone (Yao et al , ), tanshinone IIA (Zhang et al , ) and tonantzitlolone A and its synthetic enantiomer (Pfeffer et al , ). Penitrem A in MDA‐MB‐231 mammary cancer cells exerted antiproliferative, antimigratory and total β‐catenin suppressing effects (Sallam et al , ).…”

“…The other antiproliferative 700 M.T. ISLAM and apoptosis-inducing diterpenes are pseudolaric acid B (Yu et al, 2015), oridonin (Yang et al, 2015a), pseudolaric acid B (Li and Hong, 2015), crypotanshinone (Yao et al, 2015b), tanshinone IIA (Zhang et al, 2016b) and tonantzitlolone A and its synthetic enantiomer (Pfeffer et al, 2016). Penitrem A in MDA-MB-231 mammary cancer cells exerted antiproliferative, antimigratory and total β-catenin suppressing effects (Sallam et al, 2013).…”

Comparative Study on the Content and Cytotoxicity of Pseudolaric Acid B in the Five Plant Parts of Pseudolarix kaempferi

“…7 Moreover, the promising activities of pseudolaric acid B have been reviewed. 8 Anti-cancer activities can be expected since pseudolaric acids are highly cytotoxic on cancer cell lines.…”