title: Ixeris dentata (Thunb. Ex Thunb.) Nakai Extract Inhibits Proliferation and Induces Apoptosis in Breast Cancer Cells through Akt/NF-κB Pathways.
abstract: Ixeris dentata (Thunb. Ex Thunb.) Nakai (ID) exhibits various physiological activities, and its related plant derived-products are expected to represent promising cancer therapeutic agents. However, the anticancer effects of ID extract on breast cancer cells classified as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) are still unknown. In this study, we investigated the anti-cancer effects and analyzed the molecular mechanism of ID extract in T47D, MCF-7 (ER-, PR-positive, HER2-negative), SK-BR-3(ER-, PR-negative, HER2-positive), and MDA-MB-231 (Triple-negative) through in vitro studies. Additionally, we examined its anti-tumor effects through in vivo studies. Our findings indicated that ID extract-induced apoptosis was mediated via various survival pathways on four breast cancer cells by identifying the factors including Bcl-2 family, phospho-Akt and phospho-nuclear factor-κB (NF-κB). Based on in vitro findings that induced apoptosis via Akt-NF-κB signaling, we investigated the effects of ID extract on mice bearing MDA-MB-231 cells. The results showed that ID extract significantly decreased MDA-MB-231 tumor volume and weight via inducing apoptosis by suppressing phospho-Akt. Overall, these results indicate that ID extract induces apoptosis through the Akt-NFκB signaling pathway in MDA-MB-231 breast cancer cells and tumors, and it may serve as a therapeutic agent for triple-negative human breast cancer.
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 32439, Korea. shinsaya@naver.com.
authors.forename: Seong-Ah
authors.initials: SA
authors.lastname: Shin
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 32439, Korea. lhn2726@naver.com.
authors.forename: Hae-Nim
authors.initials: HN
authors.lastname: Lee
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 32439, Korea. dlscjsgkszkf@naver.com.
authors.forename: Gang-Sik
authors.initials: GS
authors.lastname: Choo
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 32439, Korea. tigershout@kongju.ac.kr.
authors.forename: Hyeong-Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Biomedical Center for Animal Resource Development, Seoul National University College of Medicine, Seoul 03080, Korea. casache@snu.ac.kr.|Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Korea. casache@snu.ac.kr.
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Che
authors.affiliation: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan 32439, Korea. wangza@kongju.ac.kr.
authors.forename: Ji-Youn
authors.initials: JY
authors.lastname: Jung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D019394:Ki-67 Antigen / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D019394:Ki-67 Antigen; D016328:NF-kappa B; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Ixeris dentata; NF-κB; apoptosis; breast cancer