ArticleTumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine2016
Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo.
Article in Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 24 citations in OpenAlex.
- RCC1 Domain-Containing Protein 1 Promotes Colon Cancer Malignant Progression by Activating Autophagy-Dependent WNT5A Secretion in Cancer-Associated Fibroblasts.Journal of the Royal Society of New Zealand · 2026Article
- Targeting protein synthesis pathways in MYC-amplified medulloblastoma.Discover oncology · 2025Review
- Anti-Cancer Strategy Based on Changes in the Role of Autophagy Depending on the Survival Environment and Tumorigenesis Stages.Molecules (Basel, Switzerland) · 2024Review
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Targeting autophagy in disease: established and new strategies.Autophagy · 2022Article
- The PI3K/AKT/mTOR signaling pathway inhibitors enhance radiosensitivity in cancer cell lines.Molecular biology reports · 2021Review
- Targeting Autophagy in Breast Cancer.International journal of molecular sciences · 2020Review
- Overexpression of ABCB1 Transporter Confers Resistance to mTOR Inhibitor WYE-354 in Cancer Cells.International journal of molecular sciences · 2020Article
- The role of RICTOR amplification in targeted therapy and drug resistance.Molecular medicine (Cambridge, Mass.) · 2020Review
- Combination of an Autophagy Inducer and an Autophagy Inhibitor: A Smarter Strategy Emerging in Cancer Therapy.Frontiers in pharmacology · 2020Review
- WYE-354 restores Adriamycin sensitivity in multidrug-resistant acute myeloid leukemia cell lines.Oncology reports · 2019Article
- CK2 inhibition with silmitasertib promotes methuosis-like cell death associated to catastrophic massive vacuolization of colorectal cancer cells.Cell death & disease · 2019Article
- Chemical modulation of autophagy as an adjunct to chemotherapy in childhood and adolescent brain tumors.Oncotarget · 2018Review
- miR-199a-3p Modulates MTOR and PAK4 Pathways and Inhibits Tumor Growth in a Hepatocellular Carcinoma Transgenic Mouse Model.Molecular therapy. Nucleic acids · 2018Article
- Article
- AT7867 Inhibits Human Colorectal Cancer Cells via AKT-Dependent and AKT-Independent Mechanisms.PloS one · 2017Article
- PKD knockdown inhibits pressure overload-induced cardiac hypertrophy by promoting autophagy via AKT/mTOR pathway.International journal of biological sciences · 2017Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 are frequently dysregulated in human colon cancers. In the present study, we evaluated the potential anti-colon cancer cell activity by a novel mTORC1/2 dual inhibitor WYE-354. We showed that WYE-354 was anti-survival and anti-proliferative when adding to primary (patient-derived) and established (HCT-116, HT-29, Caco-2, LoVo, and DLD-1 lines) colon cancer cells. In addition, WYE-354 treatment activated caspase-dependent apoptosis in the colon cancer cells. Mechanistically, WYE-354 blocked mTORC1 and mTORC2 activation. Meanwhile, it also induced autophagy activation in the colon cancer cells. Autophagy inhibitors (bafilomycin A1 and 3-methyladenine), or shRNA-mediated knockdown of autophagy elements (Beclin-1 and ATG-5), remarkably sensitized WYE-354-mediated anti-colon cancer cell activity in vitro. Further studies showed that WYE-354 administration inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Importantly, its activity in vivo was further potentiated with co-administration of the autophagy inhibitor 3-MA. Phosphorylations of Akt (Ser-473) and S6 were also decreased in WYE-354-treated HT-29 xenografts. Together, these pre-clinical results demonstrate the potent anti-colon cancer cell activity by WYE-354, and its activity may be further augmented with autophagy inhibition.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.