The Antitumor Effect of Timosaponin A3 through c-Myc Inhibition in Colorectal Cancer Cells and Combined Treatment Effect with 5-FU or Doxorubicin
| Autor: | Hyun Min Ko, Wona Jee, Do-il Park, Kwan-Il Kim, Ji Hoon Jung, Hyeung-Jin Jang |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Caspase 3
Organic Chemistry Apoptosis General Medicine Poly(ADP-ribose) Polymerase Inhibitors Saponins HCT116 Cells Catalysis Computer Science Applications Inorganic Chemistry Repressor Proteins Doxorubicin Timosaponin A3 c-Myc CNOT2 MID1IP1 HCT116 Cell Line Tumor Colonic Neoplasms Humans Steroids Fluorouracil Physical and Theoretical Chemistry Colorectal Neoplasms Molecular Biology Spectroscopy Cell Proliferation |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 11900 |
| ISSN: | 1422-0067 |
| Popis: | Timosaponin A3 (TA3), extracted from the rhizome of Anemarrhenaasphodeloides Bunge, has been reported to affect various diseases, such as cancer, Alzheimer’s disease, and allergies. However, the underlying molecular mechanisms and impacts are largely unknown. In the present study, we hypothesized that TA3 induces apoptosis through the inhibition of c-Myc expression via CNOT2 or MID1IP1 in HCT116. An MTT assay and colony formation assay were used to measure cell viability and proliferation. The protein expression of apoptotic markers and oncogenes was measured using immunoblotting and immunofluorescence assays. The interaction between MID1IP1 and c-Myc was confirmed by performing an immunoprecipitation assay. TA3 markedly inhibited colon cancer cell proliferation. Consistently, TA3 regulated the apoptotic proteins pro-PARP and caspase 3. TA3 inhibited the half-life of c-Myc and suppressed its expression in response to serum stimulation. In addition, TA3 enhanced the apoptotic effects of doxorubicin and 5-FU in colon cancer cells. Altogether, our results reveal a mechanism by which TA3 induces apoptosis through inhibiting c-Myc expression via CNOT2 or MID1IP1 in HCT116, which may help in the development of new therapies for colon cancer based on TA3 in the future. |
| Databáze: | OpenAIRE |
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