Isolinderalactone enhances the inhibition of SOCS3 on STAT3 activity by decreasing miR-30c in breast cancer.

Abstract

Development of an efficient treatment for triple-negative breast cancer is an urgent issues. Compounds from plant extracts are a potential source of novel cancer treatment. Isolinderalactone, a kind of sesquiterpenoids compound, was purified from the root of Lindera strychnifolia and Neolitsea daibuensis and shows anti-inflammatory and anticancer capacity. In the present study, isolinderalactone induced apoptosis in MDA-MB-231 cells which is a kind of triple-negative breast cancer cell line through induction of an intrinsic mitochondria-mediated and caspase-independent cell death. Treatment of isolinderalactone increased the protein level of the suppressor of cytokine signaling 3 (SCOS3), decreased phosphorylation of the signal transducer and activator of transcription 3 (STAT3), and suppressed expression of the down-stream genes of the X-linked inhibitor of apoptosis protein in MDA-MB-231 cells. Our results further showed that the level of SOCS3 expression was induced by isolinderalactone due to inhibiting the microRNA hsa-miR-30c-5p (miR-30c) expression. In addition, intraperitoneal injection of isolinderalactone induced apoptosis in a xenograft breast tumor while it did not significantly affect the histology of liver, kidney and lung of the treated mice. In conclusion, isolinderalactone induces apoptosis in MDA-MB‑231 cells and suppresses STAT3 signaling pathway through regulation of SOCS3 and miR-30c. It may become a novel treatment for triple-negative breast cancer in the future.

• Authors: Meng-Chi Yen, Ying-Chu Shih, Ya-Ling Hsu, En-Shyh Lin, Yi-Shiuan Lin, Eing-Mei Tsai, Ya-Wen Ho, Ming-Feng Hou, Po-Lin Kuo
• Journal: Oncology reports (Oncol Rep) Vol. 35 Issue 3 Pg. 1356-64 (Mar 2016) ISSN: 1791-2431 [Electronic] Greece
• PMID: 26707189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN30b microRNA, human
• MicroRNAs
• SOCS3 protein, human
• STAT3 Transcription Factor
• STAT3 protein, human
• Sesquiterpenes
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins
• X-Linked Inhibitor of Apoptosis Protein
• XIAP protein, human
• linderalactone

Topics

• Animals
• Apoptosis (drug effects)
• Cell Proliferation (drug effects)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lindera (chemistry)
• Mice
• MicroRNAs (biosynthesis, genetics)
• STAT3 Transcription Factor (biosynthesis, genetics)
• Sesquiterpenes (administration & dosage)
• Signal Transduction (drug effects)
• Suppressor of Cytokine Signaling 3 Protein
• Suppressor of Cytokine Signaling Proteins (biosynthesis, genetics)
• Triple Negative Breast Neoplasms (drug therapy, genetics, pathology)
• X-Linked Inhibitor of Apoptosis Protein (biosynthesis, genetics)
• Xenograft Model Antitumor Assays