Curcumin Mediates Its Anti-Breast Cancer Effects through the PI3K/AKT/mTOR Pathway
Introduction Breast cancer is the most common form of cancer in women and its pathogenesis is associated with diet.1 Curcumin, a flavonoid polyphenol, is a compound derived from the spice turmeric, which has been studied for its anti-carcinogenic properties.2 The PI3K, AKT, mTOR pathway is an intricate intracellular pathway that plays a role in signaling, tumorigenesis, and cell proliferation in breast cancer cells.3 Curcumin may mediate its anti-carcinogenic properties in breast cancer cells, in part, through the PI3K/AKT/mTOR pathway.1–4 Methods T47D and MCF7 breast cancer cell lines treated with 10 uM and 30 uM of curcumin for 24 hours and cell cycle arrest was measured using flow cytometry. Apoptosis was measured using annexin V and propodium iodide staining. Western blot analysis was used to study phosphorylation patterns of PI3K, AKT, and mTOR.1 Investigators measured LC3I/II, a marker for autophagy, using western blot.3 Chromatin immunoprecipitation was used to quantify expression of Sp1 and NF-YA transcription factors.4 Researchers also conducted a randomized, double-blind, placebo-controlled comparative clinical study. One hundred and fifty women with breast cancer received treatment of paclitaxel with curcumin or paclitaxel with placebo intravenously. Outcomes were measured using objective response rate (ORR).5 In all experiments, phosphorylation of element of the PI3K, AKT, mTOR pathways was measured using western blot analysis.1-5 Results Curcumin was found to increase cell cycle arrest and apoptosis in T47D and MCF7 breast cancer cell lines. Curcumin induced autophagic degradation activity (known as autophagic flux). Additionally, LC3II levels increased in curcumin-treated cells, in comparison to controls which led investigators to conclude that curcumin-induced complete autophagy.2 Decreased expression of the AKT and mTOR led to decreased expression of the Sp1 and NF-YA transcription factors. 4 Researchers found that the ORR of curcumin was significantly higher than that of the placebo at 4 weeks follow-up. After treatment, the ORR of curcumin was significantly higher than that of placebos. The self-examined physical performance of patients who took the curcumin was significantly higher than patients who received the placebo.5 Conclusion Curcumin inhibits the PI3K/AKT/mTOR pathway leading to a variety of antitumorigenic downstream effects including; promoting cell cycle arrest and apoptosis, autophagic degradation, and decreased expression of pro-proliferative transcription factors. Clinical efficacy of curcumin may be limited due to it not having a significantly higher ORR at 12 weeks after treatment. Further clinical studies using curcumin as an adjuvant therapeutic may be warranted.
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- Arena A, Romeo MA, Benedetti R, et al. New insights into curcumin-and resveratrol-mediated anti-cancer effects. Pharmaceuticals. 2021;14(11). doi:10.3390/ph14111068
- Badr G, Gul HI, Yamali C, et al. Curcumin analogue 1,5-bis(4-hydroxy-3-((4-methylpiperazin-1-yl)methyl)phenyl)penta-1,4-dien-3-one mediates growth arrest and apoptosis by targeting the PI3K/AKT/mTOR and PKC-theta signaling pathways in human breast carcinoma cells. Bioorg Chem. 2018;78:46-57. doi:10.1016/j.bioorg.2018.03.006
- Chatterjee B, Ghosh K, Suresh L, Kanade SR. Curcumin ameliorates PRMT5-MEP50 arginine methyltransferase expression by decreasing the Sp1 and NF-YA transcription factors in the A549 and MCF-7 cells. Mol Cell Biochem. 2019;455(1-2):73-90. doi:10.1007/s11010-018-3471-0
- Saghatelyan T, Tananyan A, Janoyan N, et al. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine. 2020;70(March):153218. doi:10.1016/j.phymed.2020.153218