Background: Cancer stem cells (CSCs) play a key role in tumor cell growth, drug resistance, recurrence, and metastasis. Proanthocyanidins (PC) is widely existed in plants and endowed with powerful antioxidant and anti-aging effects. Interestingly, recent studies have found that PC exhibits the inhibitory effect on tumor growth. However, the role of PC in CSCs of colorectal cancer (CRC) and molecular mechanism remain unclear.
Methods: CCK-8, colony, and tumorsphere formation assay were used to evaluate cancer cell viability and stemness, respectively. Western blotting was used to detect the protein expression. Tumor xenograft experiments were employed to examine the tumorigenicity of CRC cells in nude mice.
Results: PC decreased the proliferation of CRC cells (HT29 and HCT-116), and improved the sensitivity of CRC cells to oxaliplatin (L-OHP), as well as inhibited tumor growth in nude mice. Further studies showed that PC also down-regulated CSCs surface molecular and stemness transcriptional factors, while suppressed the formations of tumorspheres and cell colony in CRC. In addition, PC-impaired proteins expressions of p-GSK3β, β-catenin and DVL1-3. LiCl, an activator of the Wnt/β-catenin signaling, rescued PC-induced downregulation of CSCs markers, and reduction of tumorspheres and cell colony formation abilities in CRC cells. Furthermore, the effects of PC on inhibiting cell proliferation and enhancing L-OHP sensitivity were impaired by LiCl.
Conclusions: PC exerted an inhibitory effect on CSCs via Wnt/β-catenin in CRC, and may be a potential new class of natural drug for CRC treatment.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/tox.23924 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Susceptibility of different mice species to chemical induction of colorectal cancer by 1,2-dimethylhydrazine.
J Egypt Natl Canc Inst
January 2025
Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt.
Background: Colorectal cancer (CRC) is a major public health concern. Animal models play a crucial role in understanding the disease pathology and development of effective treatment strategies. Chemically induced CRC represents a cornerstone in animal model development; however, due to the presence of different animal species with different genetic backgrounds, it becomes mandatory to study the susceptibility of different mice species to CRC induction by different chemical entities such as 1,2-dimethylhydrazine (DMH).
View Article and Find Full Text PDFHDAC and MEK inhibition synergistically suppresses HOXC6 and enhances PD-1 blockade efficacy in BRAF-mutant microsatellite stable colorectal cancer.
J Immunother Cancer
January 2025
Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, Beijing, China
Background: B-Raf proto-oncogene, serine/threonine kinase (BRAF)-mutant microsatellite stable (MSS) colorectal cancer (CRC) constitutes a distinct CRC subgroup, traditionally perceived as minimally responsive to standard therapies. Recent clinical attempts, such as BRAF inhibitors (BRAFi) monotherapy and combining BRAFi with other inhibitors, have yielded unsatisfactory efficacy. This study aims to identify a novel therapeutic strategy for this challenging subgroup.
View Article and Find Full Text PDFPlatinum micromotors for mucosal penetration and colorectal cancer therapy.
Int J Pharm
January 2025
Clinical Center for Tumor Therapy, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China. Electronic address:
The therapeutic outcomes of medications were restricted by the colonic mucosal barrier during the treatment of colorectal cancer (CRC). Micro/nanomotors can overcome the mucus barriers to reach deep colorectal tumors. In this study, we constructed a novel microsized PLGA-Pt micromotor (MM) driven by hydrogen peroxide (HO) to enhance drug delivery to the CRC tissues and achieve effective antitumor therapy.
View Article and Find Full Text PDFAtractylenolide I (ATL-I) can interfere with Colorectal cancer (CRC) cell proliferation by changing apoptosis, glucose metabolism and other behaviors, making it an effective drug for inhibiting CRC tumor growth. In this paper, we investigated the interactions between ATL-I and Keratin 7 (KRT7), a CRC-specific marker, to determine the potential pathways by which ATL-I inhibits CRC development. The KRT7 expression level in CRC was predicted online using the GEPIA website and then validated.
View Article and Find Full Text PDFSTAT3-related lncRNAs in colorectal cancer progression; Special focus on immune cell's evasion.
Pathol Res Pract
January 2025
Medical laboratory technique college, the Islamic University, Najaf, Iraq; Medical laboratory technique college, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq.
Colorectal cancer (CRC) is globally ranked as the third leading cause of cancer-related deaths in both men and women. There is an urgent need for novel biomarkers to facilitate early diagnosis and enhance patient care, thereby improving treatment response and reducing mortality rates. Signal transducer and activator of transcription 3 (STAT3) is essential for controlling the anti-tumor immune response since it is a hub for several oncogenic signaling pathways.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!