4.4 Article

Costunolide and dehydrocostuslactone from Saussurea lappa root inhibit autophagy in hepatocellular carcinoma cells

Journal

JOURNAL OF NATURAL MEDICINES
Volume 75, Issue 1, Pages 240-245

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s11418-020-01462-1

Keywords

Autophagy; Saussurea lappa; Costunolide; Dehydrocostuslactone; Hepatocellular carcinoma

Funding

  1. Sasakawa Scientific Research Grant from The Japan Science Society [2018-4039]
  2. JSPS KAKENHI [19K07145, 25871011]
  3. Grants-in-Aid for Scientific Research [25871011, 19K07145] Funding Source: KAKEN

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The study found that CL and DCL from the root of Saussurea lappa inhibit the autophagy process in HepG2 cells, leading to the accumulation of LC3 and p62. These results suggest the potential of CL and DCL as autophagy inhibiting agents for liver cancer therapy, warranting further investigation.
Autophagy is a catabolic process for degradation of intracellular components and plays an important role in the development and growth of cancer. Our preliminary screening confirmed that an extract from the root of Saussurea lappa remarkably suppressed the proliferation of HepG2 hepatocellular carcinoma cells and inhibited autophagy. In this study, we explored the effects of costunolide (CL) and dehydrocostuslactone (DCL), which are bioactive sesquiterpene lactones in this extract, on autophagy modulation in HepG2 cells. An analysis of autophagy-related proteins demonstrated that CL and DCL blocks the autophagy process that leads to the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and SQSTM1/p62 (p62). LC3 turnover assays indicated that CL and DCL trigger autophagy inhibition by blocking the autophagic flux, thereby resulting in the accumulation of LC3-II and p62. These results are encouraging and warrant further study of CL and DCL for potential use as autophagy inhibiting agents for liver cancer therapy.

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