ArticleMolecular and cellular biochemistry2015
Synergistic anticancer effects of combined γ-tocotrienol and oridonin treatment is associated with the induction of autophagy.
Article in Molecular and cellular biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 41 citations in OpenAlex.
- Research progress on the signaling pathway mechanism of terpenoids against breast cancer.Discover oncology · 2025Review
- Dual role of autophagy in bone metastasis: mechanistic insights and therapeutic targeting.American journal of clinical and experimental urology · 2025Review
- Oridonin fromFood science & nutrition · 2024Review
- Targeting autophagy for breast cancer prevention and therapy: From classical methods to phytochemical agents.Iranian journal of basic medical sciences · 2024Review
- Terpenoids' anti-cancer effects: focus on autophagy.Apoptosis : an international journal on programmed cell death · 2021Review
- Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.International journal of molecular sciences · 2021Review
- Oridonin and its derivatives for cancer treatment and overcoming therapeutic resistance.Genes & diseases · 2021Review
- Novel Approaches of Dysregulating Lysosome Functions in Cancer Cells by Specific Drugs and Its Nanoformulations: A Smart Approach of Modern Therapeutics.International journal of nanomedicine · 2021Review
- Oridonin: A Review of Its Pharmacology, Pharmacokinetics and Toxicity.Frontiers in pharmacology · 2021Review
- Cellular Mechanisms of Circulating Tumor Cells During Breast Cancer Metastasis.International journal of molecular sciences · 2020Review
- Prevention of renal ischemia and reperfusion injury by penehyclidine hydrochloride through autophagy activation.Molecular medicine reports · 2020Article
- Tocotrienols Modulate a Life or Death Decision in Cancers.International journal of molecular sciences · 2019Review
- Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.Chinese medicine · 2019Review
- Synergistic Anticancer Effect of Tocotrienol Combined with Chemotherapeutic Agents or Dietary Components: A Review.International journal of molecular sciences · 2016Review
- γ-Tocotrienol reversal of epithelial-to-mesenchymal transition in human breast cancer cells is associated with inhibition of canonical Wnt signalling.Cell proliferation · 2016Article
- Penfluridol suppresses pancreatic tumor growth by autophagy-mediated apoptosis.Scientific reports · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
γ-Tocotrienol and oridonin are natural phytochemicals that display potent anticancer activity. Studies showed that combined treatment with subeffective doses of γ-tocotrienol with oridonin resulted in synergistic autophagic and apoptotic effects in malignant +SA, but not normal CL-S1 mouse mammary epithelial cells in vitro. Specifically, combined treatment with low doses of γ-tocotrienol (8 µM) and oridonin (2 µM) for 24 h resulted in synergistic inhibition of +SA mammary cancer cells viability. This combination significantly enhanced the expression of autophagy cellular markers including the conversion of LC3B-I to LC3B-II, beclin-1, Atg3, Atg7, Atg5-Atg12, LAMP-1 and cathepsin-D, and pretreatment with the autophagy inhibitors 3-methyladenine (3-MA) or bafilomycin A1 (Baf1) blocked these effects. Furthermore, blockade of γ-tocotrienol and oridonin-induced autophagy with 3-MA or Baf1 induced a modest, but significant reduction in cytotoxicity resulting from the combined treatment of these phytochemicals. The anticancer effects of combination treatment was also associated with a large suppression in Akt/mTOR mitogenic signaling and corresponding increase in the levels of apoptotic cellular marker including cleaved caspase-3 and PARP, and Bax/Bcl-2 ratio in these tumor cells. These effects were also found to be selective against cancer cells, since similar combined treatment with γ-tocotrienol and oridonin did not induce autophagy or reduce viability of normal mouse CL-S1 mammary epithelial cells. These findings indicate that combined γ-tocotrienol and oridonin-induced autophagy plays a role in mediating the synergistic anticancer effects of these phytochemicals.
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