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Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway

Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
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Int. J. Mol. Sci. 2018, 19(9), 2739; https://doi.org/10.3390/ijms19092739
Received: 2 August 2018 / Revised: 6 September 2018 / Accepted: 6 September 2018 / Published: 13 September 2018
(This article belongs to the Section Biochemistry)
Cryptotanshinone (CTT) is a natural product and a quinoid diterpene isolated from the root of the Asian medicinal plant, Salvia miltiorrhizabunge. Notably, CTT has a variety of anti-cancer actions, including the activation of apoptosis, anti-proliferation, and reduction in angiogenesis. We further investigated the anti-cancer effects of CTT using MTS, LDH, and Annexin V assay, DAPI staining, cell cycle arrest, and Western blot analysis in NSCLC cell lines. NSCLC cells treated with CTT reduced cell growth through PI3K/Akt/GSK3β pathway inhibition, G0/G1 cell cycle arrest, and the activation of apoptosis. CTT induced an increase of caspase-3, caspase-9, poly-ADP-ribose polymerase (PARP), and Bax, as well as inhibition of Bcl-2, survivin, and cellular-inhibitor of apoptosis protein 1 and 2 (cIAP-1 and -2). It also induced G0/G1 phase cell cycle arrest by decreasing the expression of the cyclin A, cyclin D, cyclin E, Cdk 2, and Cdk 4. These results highlight anti-proliferation the latent of CTT as natural therapeutic agent for NSCLC. Therefore, we investigated the possibility of CTT as an anti-cancer agent by comparing with GF, which is a representative anti-cancer drug. View Full-Text
Keywords: cryptotanshinone; NSCLC; cell cycle arrest; apoptosis; PI3K/Akt/GSK3β cryptotanshinone; NSCLC; cell cycle arrest; apoptosis; PI3K/Akt/GSK3β
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Kim, S.-A.; Kang, O.-H.; Kwon, D.-Y. Cryptotanshinone Induces Cell Cycle Arrest and Apoptosis of NSCLC Cells through the PI3K/Akt/GSK-3β Pathway. Int. J. Mol. Sci. 2018, 19, 2739.

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