Tanshinone I regulates autophagic signaling via the activation of AMP-activated protein kinase in cancer cells

This study aims to investigate whether AMP-activated protein kinase dependent pathway is involved in the autophagic signaling regulation and its relationship with tumor suppression. Breast cancer cells (MDA-MB-231, MCF-7) and hepatocellular carcinoma cells (HepG2) were treated with Tanshinone I or vehicle. Acridine orange dyeing and transmission electron microscopy were employed to evaluate autophagic cells. MTT and Cell Counting Kit-8 assays were used to detect the effect of Tanshinone I combined with autophagy inhibitors on cell proliferation. Western blot was used to detect the expression levels of Beclin1 and LC3-I/II, as well as the phosphorylation of AMPKα and ULK1. Our results showed that Tanshinone I suppressed proliferation of HepG2, MDA-MB-231 and MCF-7 cancer cell lines. LC3-II and P62 were induced by Tanshinone I in all three cancer cell lines. But autophagic flux analysis showed that Tanshinone I treatment induced autophagy only in MDA-MB-231, which was also proved by transmission electron microscopy. Tanshinone I upregulated the phosphorylation of AMPKα and its downstream ULK1. AMP-activated protein kinase inhibitor compound C attenuated Beclin 1 and LC3-II expression induced by Tanshinone I in HepG2. In MDA-MB-231, compound C surprisingly induced LC3-II upregulation which is independent of AMPKα activation. Under this circumstance, treatment of Tanshinone I combined with compound C significantly inhibited MDA-MB-231 proliferation, compared with Tanshinone I ...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research