Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition

Siddiqui, Farid Ahmad; Prakasam, Gopinath; Chattopadhyay, Shilpi; Rehman, Asad Ur; Padder, Rayees Ahmad; Ansari, Mohammad Afaque; Irshad, Rasha; Mangalhara, Kailash Chandra; Bamezai, R.; Husain, Mohammad; Syed, Mansoor Ali; Iqbal, Mohammad Askandar

doi:10.1038/s41598-018-25524-3

Cited by 120 publications

(106 citation statements)

References 62 publications

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“…They showed that a decrease of PKM2 (mediated by curcumin or by targeted PKM2 silencing) significantly reduces aerobic glycolysis and is also consequential for cell survival. Curcumin's influence on PKM1 was not addressed, and the effect was not shown as cell-type specific [22]. We wanted to explore the effect of curcumin on both isoforms in four different cancer -originating cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Siddiqui et al have recently reported that curcumin downregulates PKM2 expression in cancer cells, consequently decreasing the Warburg effect. The PKM2 downregulation coincided with the inhibition of the mammalian target of rapamycin (mTOR) pathway and consequential downregulation of hypoxia-inducible factor 1-alpha HIF1α [22]. Previously, PKM2 transcription has been shown to be activated on PI3K/mTOR-mediated HIF1α induction [23].…”

Section: Introductionmentioning

confidence: 93%

“…Based on these two assays we have chosen 20 µM concentration of curcumin, which exerted considerable inhibitory effects on proliferation, without inducing the high level of MTT recordable cytotoxicity, in 96-well plates. This concentration is the same as the curcumin concentration that was used by other authors studying the effects of curcumin on cancer cell metabolism [22]. As a "solvent control" reactions, the final concentration of ethanol was equal to the final ethanol concentration (0.2%) added from curcumin solution.…”

Section: Cell Lines and Cell Culture Conditionsmentioning

confidence: 99%

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Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

Mojzeš

Tomljanović

Milković

et al. 2020

IJMS

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In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been shown to interact with multiple molecules and signaling pathways in cancer cells, including those relevant for cell metabolism. The effect of curcumin and its solvent, ethanol, was explored on four different cancer cell lines, in which the Warburg effect varied. Vital cellular parameters (proliferation, viability) were measured along with the glucose consumption and lactate production. The transcripts of pyruvate kinase 1 and 2 (PKM1, PKM2), serine hydroxymethyltransferase 2 (SHMT2) and phosphoglycerate dehydrogenase (PHGDH) were quantified with RT-qPCR. The amount and intracellular localization of PKM1, PKM2 and signal transducer and activator of transcription 3 (STAT3) proteins were analyzed by Western blot. The response to ethanol and curcumin seemed to be cell-type specific, with respect to all parameters analyzed. High sensitivity to curcumin was present in the cell lines originating from head and neck squamous cell carcinomas: FaDu, Detroit 562 and, especially, Cal27. Very low sensitivity was observed in the colon adenocarcinoma-originating HT-29 cell line, which retained, after exposure to curcumin, a higher levels of lactate production despite decreased glucose consumption. The effects of ethanol were significant.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

Section: Cell Lines and Cell Culture Conditionsmentioning

confidence: 99%

See 1 more Smart Citation

Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

Mojzeš

Tomljanović

Milković

et al. 2020

IJMS

View full text Add to dashboard Cite

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“…Curcumin and its analogues are shown to be emerging as effective agents for the treatment of several malignant diseases such as cancer. Numerous studies have shown that curcumin and its preparations can inhibit tumors in almost all parts of the body, including head and neck, ovarian, skin and gastric cancers [15][16][17][18][19][20].…”

Section: Curcuminmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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“…Tumor cells as well as TEC heavily depend on glycolysis (Warburg effect) for their energy requirements. Curcumin, an extensively studied polyphenolic compound, decreases glycolysis via dowregualting key glycolytic enzyme PKM2 via inhibiting mTOR/HIF-1α [121]. It up-regulates the PTEN expression via miRNA-21, thereby negatively regulating the PI3K/AKT pathway that regulates survival and glycolysis [122].…”

Section: Plant Compounds Targeting Metabolism Regulating Mirnamentioning

confidence: 99%

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

et al. 2020

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Several phytochemicals have been identified for their role in modifying miRNA regulating tumor progression. miRNAs modulate the expression of several oncogenes and tumor suppressor genes including the genes that regulate tumor angiogenesis. Hypoxia inducible factor-1 alpha (HIF-1α) signaling is a central axis that activates oncogenic signaling and acts as a metabolic switch in endothelial cell (EC) driven tumor angiogenesis. Tumor angiogenesis driven by metabolic reprogramming of EC is crucial for tumor progression and metastasis in many different cancers, including breast cancers, and has been linked to aberrant miRNA expression profiles. In the current article, we identify different miRNAs that regulate tumor angiogenesis in the context of oncogenic signaling and metabolic reprogramming in ECs and review how selected phytochemicals could modulate miRNA levels to induce an anti-angiogenic action in breast cancer. Studies involving genistein, epigallocatechin gallate (EGCG) and resveratrol demonstrate the regulation of miRNA-21, miRNA-221/222 and miRNA-27, which are prognostic markers in triple negative breast cancers (TNBCs). Modulating the metabolic pathway is a novel strategy for controlling tumor angiogenesis and tumor growth. Cardamonin, curcumin and resveratrol exhibit their anti-angiogenic property by targeting the miRNAs that regulate EC metabolism. Here we suggest that using phytochemicals to target miRNAs, which in turn suppresses tumor angiogenesis, should have the potential to inhibit tumor growth, progression, invasion and metastasis and may be developed into an effective therapeutic strategy for the treatment of many different cancers where tumor angiogenesis plays a significant role in tumor growth and progression.

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Curcumin decreases Warburg effect in cancer cells by down-regulating pyruvate kinase M2 via mTOR-HIF1α inhibition

Cited by 120 publications

References 62 publications

Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Anti-Angiogenic Effects of Phytochemicals on miRNA Regulating Breast Cancer Progression

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