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Extracts from the Perilla frutescens var. (Odash.) Kudo leaves have anti-tumor effects on the breast cancer cell via suppression of the YAP activity
- Author(s)
- 김초롱
- Alternative Author(s)
- Cho-Long Kim
- Advisor
- 모정순
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2020-08
- Language
- eng
- Keyword
- Hippo pathway; Perilla
- Alternative Abstract
- The Hippo signaling pathway plays a critical role in cell proliferation, apoptosis, differentiation, and development. It has emerged as a key signal transduction pathway that regulates various biological functions in many different types of tumors. Yes-associated protein (YAP) and WW domain-containing transcription regulator protein (TAZ) are the major effectors of the Hippo signaling pathway, which have been observed in many types of cancer. Furthermore, functional dysregulation of the Hippo signaling pathway enhances the oncogenic properties of YAP and TAZ and promotes cancer development. Recently, the use of complementary and alternative medicine is rapidly increasing in Asia and Western countries. Perilla frutescens var. acuta (Odash.) Kudo leaves, a common Korean medical plant, is known to possess anti-oxidant, anti-allergic, anti-inflammatory, and tumor-preventing properties against several types of cancer. In this study, we aimed to evaluate the biological mechanisms of the anti-tumor effect of P. frutescens leaf extract (PLE) via the Hippo signaling pathway in breast cancer cells. Using the MTT assay, cell viability in breast cancer cells was reduced by PLE. Following treatment with PLE, YAP/TAZ protein levels were reduced and the biomarkers cleaved caspase-3 and poly ADP ribose polymerase (PARP) levels increased in MDA-MB-231 and BT549 cells, which are triple negative breast cancer cell lines. To elucidate the molecular mechanism of PLE on the regulation of YAP activity, we investigated the expression of YAP after PLE treatment. PLE enhanced the phosphorylation of YAP/TAZ. Furthermore, PLE suppresses YAP/TAZ transcriptional activity through the disruption of the YAP/TAZ-TEAD complex. Moreover, this activity was substantially suppressed in large tumor suppressor kinase 1/2 (LATS1/2) depletion cells compared to LATS1/2 wild-type cells. The migration rate of breast cancer cells was suppressed by PLE treatment in a time-dependent manner. This ability was weakened in cells expressing TEAD1△C-YAP (AD), which is a constitutively active form of the YAP fusion protein, suggesting that the migration inhibition effect of PLE is achieved by regulating YAP activity. Collectively, PLE diminishes growth of breast cancer cells via regulation of the Hippo signaling pathway in a LATS1/2-dependent manner, which suggests that PLE can be used as a therapeutic medical herb for breast cancer.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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