title: Goniothalamin induces apoptosis associated with autophagy activation through MAPK signaling in SK-BR-3 cells.
abstract: Goniothalamin, a plant bioactive styrly-lactone, possesses many biological activities. In the present study, the anticancer effect of goniothalamin on human breast cancer cell line SK-BR-3 was investigated. The results showed that goniothalamin induced nuclear condensation, DNA fragmentation, apoptotic bodies and mitochondrial dysfunction as determined by JC-1 staining. Goniothalamin also increased the Bax/Bcl-2 ratio and expression of cleaved caspase-7, cleaved caspase-9 and cleaved PARP, but decreased Bcl-2 expression. In addition, goniothalamin induced apoptosis via p-JNK1/2 and p-p38 upregulation and inhibited cell survival via p-ERK1/2 and p-Akt downregulation. Notably, goniothalamin induced autophagy through upregulation of Atg7, Atg12-Atg5 conjugation and LC3II. The increased p-p38 and p-JNK1/2 and decreased p-Akt may lead to autophagy induction. Therefore, goniothalamin promoted apoptosis associated with autophagy induction in SK-BR-3 cells through p-p38 and p-JNK1/2 upregulation and p-Akt downregulation. The present study indicated that goniothalamin may be further used as a potential therapeutic candidate or may offer an alternative treatment for breast cancer.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
authors.forename: Sukanda
authors.initials: S
authors.lastname: Innajak
authors.affiliation: Department of Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand.
authors.forename: Wilawan
authors.initials: W
authors.lastname: Mahabusrakum
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok 10110, Thailand.
authors.forename: Ramida
authors.initials: R
authors.lastname: Watanapokasin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D053078:Membrane Potential, Mitochondrial; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011753:Pyrones; C103280:goniothalamin; D051057:Proto-Oncogene Proteins c-akt