Bufalin induces apoptosis and autophagy via the Ca2+/CaMKKβ/AMPK/Beclin1 signaling pathway in osteosarcoma cells
Open accessAbstract
Bufalin, a major cardiotonic compound of the traditional Chinese medicine Chanshu has been used for cancer treatment for several years. However, the molecular mechanisms of Bufalin‐induced autophagy in osteosarcoma (OS) is not fully understood. In the present study, it was shown that Bufalin induced crosstalk between apoptosis and autophagy, which resulted in OS cell death. Mechanistically, Bufalin induced autophagy by increased the ratio of microtubule‐associated protein 1A/1B‐light chain 3 (LC3)‐II/LC3‐I, and inducing apoptosis via the caspase‐dependent pathway. Inhibition of autophagy promoted Bufalin‐induced cell death. In contrast, suppression of apoptosis enhanced Bufalin‐induced autophagy. In addition, it was found that Bufalin activated the Ca 2+/calmodulin‐dependent protein kinase β/AMPK/Beclin1 pathway, which resulted in induction of autophagy. These findings provide a mechanistic understanding of the means by which Bufalin mediates autophagy and apoptosis in OS cells.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Bufalin induced apoptosis, necroptosis, ferroptosis, autophagy, and senescence through AMPK, RIP1/ROS, DECR1, p62, and p53 pathways.
“Bufalin induced apoptosis, necroptosis, ferroptosis, autophagy, and senescence through AMPK, RIP1/ROS, DECR1, p62, and p53 pathways5,44–48.”
From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [46]
The Abstract and section 3.4 report bufalin-induced autophagy through the Ca²⁺/CaMKKβ/AMPK/Beclin1 pathway, and section 3.3 reports bufalin-induced apoptosis in osteosarcoma cells. The passages do not establish bufalin-induced necroptosis, ferroptosis, or senescence through RIP1/ROS, DECR1, p62, or p53; the sentence’s multiple citations do not specify which source supports those parts. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The role for autophagy in cancer
White, E. (2015) · Journal of Clinical Investigation · doi:10.1172/jci73941 · Cited by 1,332 · see citing works
Formation Process of Autophagosome Is Traced with Apg8/Aut7p in Yeast
Kirisako, T., Baba, M., Ishihara, N., Miyazawa, K., Ohsumi, M., Yoshimori, T., Noda, T., & Ohsumi, Y. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.2.435 · Cited by 881 · see citing works
Flagged first, then by citations
Research works printed but not linked: 7
- Camuzard, O., Santucci-Darmanin, S., Carle, G. F., & Pierrefite-Carle, V. (2019). Role of autophagy in osteosarcoma. Journal of Bone Oncology, 16, 100235.
- Kanzawa, T., Bedwell, J., Kondo, Y., Kondo, S., & Germano, I. M. (2003). Inhibition of DNA repair for sensitizing resistant glioma cells to temozolomide. Journal of Neurosurgery, 99, 1047-1052.
- Onoe-Takahashi, A., Suzuki-Karasaki, M., Suzuki-Karasaki, M., Ochiai, T., & Suzuki-Karasaki, Y. (2019). Autophagy inhibitors regulate TRAIL sensitivity in human malignant cells by targeting the mitochondrial network and calcium dynamics. International Journal of Oncology, 54, 1734-1746.
- Sevelda, F., Mayr, L., Kubista, B., Lötsch, D., van Schoonhoven, S., Windhager, R., Pirker, C., Micksche, M., & Berger, W. (2015). EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance. Journal of Experimental & Clinical Cancer Research, 34, 134.
- Takai, N., Kira, N., Ishii, T., Yoshida, T., Nishida, M., Nishida, Y., Nasu, K., & Narahara, H. (2012). Bufalin, a traditional oriental medicine, induces apoptosis in human cancer cells. Asian Pacific Journal of Cancer Prevention, 13, 399-402.
- Tsai, S. C., Yang, J. S., Peng, S. F., Lu, C. C., Chiang, J. H., Chung, J. G., Lin, M. W., Lin, J. K., Amagaya, S., Chung, C. W. S., Tung, T. T., Huang, W. W., & Tseng, M. T. (2012). Bufalin increases sensitivity to AKT/mTOR-induced autophagic cell death in SK-HEP-1 human hepato- cellular carcinoma cells. International Journal of Oncology, 41, 1431-1442.
- Zang, J., Zuo, D., Shogren, K. L., Gustafson, C. T., Zhou, Z., Thompson, M. A., Guo, R., Prakash, Y. S., Lu, L., Guo, W., Maran, A., & Prakash, Y. S. (2019). STIM1 expression is associated with osteosarcoma cell survival. Chinese Journal of Cancer Research, 31, 203-211.
Cited by
Sorted by citations
Jiang, S., Liu, K., Jiang, T., Li, H., Wei, X., Wan, X., Zhong, C., Gong, R., Chen, Z., Zou, C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62288-7 · Cited by 23 · see citing works
- Authors
- Zheng, Y., He, Z., Su, Z., Wang, H., Jiang, X., Fang, X., Lu, S., & Li, Y.
- Affiliations
- Guangxi Medical University (CN)
- Department of Orthopaedics Minzu Affiliated Hospital of Guangxi Medical University Nanning Guangxi Zhuang People's Republic of China
- The First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine (CN)
- Corresponding author
- Li, Yuan
- Venue
- Cell Biology International
- Publisher
- Wiley
- Published
- 2023-03-29
- Volume
- 47
- Issue
- 8
- Pages
- 1344-1353
- ISSN
- 1065-6995 (ISSN-L)
- 1095-8355
- OpenAlex
- W4361283148
- Cited by
- 10
- References
- 2
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cell Biology International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Guangxi University
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Health Sciences › Medicine › Complementary and alternative medicine › Traditional Chinese Medicine Analysis
- Keywords
- bufalin, osteosarcoma, apoptosis, autophagy, autophagy-apoptosis crosstalk, CaMKKβ, AMPK, Beclin-1, LC3-II/LC3-I ratio, caspase-dependent cell death, Ca2+/calmodulin signaling
- MeSH terms
- Beclin-1, Autophagy, Bufanolides, Calcium, Humans, Osteosarcoma, Signal Transduction, Apoptosis, Cell Line, Tumor, Calcium-Calmodulin-Dependent Protein Kinase Kinase, AMP-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
