Inorganic polyphosphate as an energy source in tumorigenesis

Boyineni, Jerusha; Margaryan, Naira V.; Demirkhanyan, Lusine; Tye, Michael; Johnson, Robert W.; González‐Nilo, Fernando; Hendrix, Mary J.C.; Pavlov, Evgeny; Soares, Marcelo B.; Zakharian, Eleonora; Malchenko, Sergey

doi:10.18632/oncotarget.27838

Cited by 10 publications

(16 citation statements)

References 52 publications

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“…The process of polyP production in mammalian cells has not been comprehensively elucidated. However, recent studies have proposed a possible mutual conversion between ATP and polyP (Baev et al, 2020; Borden et al, 2021; Boyineni et al, 2020; McIntyre & Solesio, 2021; Müller et al, 2017, 2019; Pavlov et al, 2010). Taken together, these results suggest that the polyP level is equilibrated with the ATP level in platelets.…”

Section: Discussionmentioning

confidence: 99%

Platelet polyphosphate and energy metabolism in professional male athletes (soccer players): A cross‐sectional pilot study

Ushiki

Mochizuki

Suzuki

et al. 2022

Physiological Reports

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Human platelet polyphosphate (polyP) is a multifunctional molecule; however, its functions are not yet fully understood. A recent study demonstrated that similar to skeletal muscle, polyP is involved in energy metabolism in platelets, which suggests that well-trained athletes may exhibit elevated platelet polyP levels for energy storage. To test this hypothesis, we quantified platelet polyP along with NADH, a component involved in ATP production in non-trained and well-trained male Japanese participants of the same generation. Washed platelets were prepared from the venous blood of young, healthy, non-athletes, and professional soccer players (pro-athletes). NADH and polyP levels were spectrophotometrically determined using tetrazolium reduction and fluorometrically determined using 4′,6-diamidino-2-phenylindole at the excitation/emission wavelengths of 425/525 nm. Body weight and impedances were measured simultaneously. Statistical analyses were performed using the Mann-Whitney U test and Spearman correlation coefficient. Although basal metabolic rate levels were significantly higher, platelet polyP levels were significantly lower in pro-athletes than in that in non-athletes. No significant differences were detected in other body compositions or platelet indices between the two groups. The pro-athlete group showed a moderate, nearly significant correlation (R = 0.439; p = 0.0512) between platelet polyP and NADH levels. Taken together with the weak correlation data between polyP and body mass index, it is suggested that platelet polyP levels may be influenced by platelet and body energy metabolic activity. Further biochemical studies are needed to elucidate this mechanism.

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Section: Discussionmentioning

confidence: 99%

Platelet polyphosphate and energy metabolism in professional male athletes (soccer players): A cross‐sectional pilot study

Ushiki

Mochizuki

Suzuki

et al. 2022

Physiological Reports

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“…Thus, they hypothesized that polyP directly contributes to ATP production or serves as a reservoir for high-energy phosphoryl groups to regulate enzymatic activity rates. Several research groups subsequently supported this finding [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 79%

“…However, the cellular levels of polyP are highly dynamic and respond rapidly to various inhibitors and activators of mitochondrial respiration [ 6 ]. PolyP production is closely related to the energetic state of the mitochondria, that is, the presence of ATP and the activity of mitochondrial F 0 F 1 -ATP synthase [ 2 , 17 , 18 , 19 , 20 ]. ATP synthase is a key enzyme in polyP hydrolysis.…”

Section: Discussionmentioning

confidence: 99%

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Modulation of ATP Production Influences Inorganic Polyphosphate Levels in Non-Athletes’ Platelets at the Resting State

Ushiki

Mochizuki

Suzuki

et al. 2022

IJMS

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Platelets produce inorganic polyphosphate (polyP) upon activation to stimulate blood coagulation. Some researchers have linked polyP metabolism to ATP production, although the metabolic linkage is yet to be elucidated. We found evidence for this possibility in our previous study on professional athletes (versus non-athletes), and proposed that the regulatory mechanism might be different for these two groups. To explore this aspect further, we investigated the effects of modulated ATP production on polyP levels. Blood samples were obtained from Japanese healthy, non-athletes in the presence of acid-citrate-dextrose. The platelets in the plasma were treated with oligomycin, rotenone, and GlutaMAX to modulate ATP production. PolyP level was quantified fluorometrically and visualized using 4′,6-diamidino-2-phenylindole. Correlations between polyP and ATP or NADH were then calculated. Contrary to the hypothesis, inhibitors of ATP production increased polyP levels, whereas amino acid supplementation produced the opposite effect. In general, however, polyP levels were positively correlated with ATP levels and negatively correlated with NADH levels. Since platelets are metabolically active, they exhibit high levels of ATP turnover rate. Therefore, these findings suggest that ATP may be involved in polyP production in the resting platelets of non-athletes.

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“…numerous physiological and remarkable functions of polyP as a potential drug [6][7][8][9][10][11]. In our previous study, we reported the polyP treatment in non-small lung cancer cell lines, specifically H1299, increased the number of double-stranded breaks after X-ray irradiation and enhanced their radiosensitivity [12].…”

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confidence: 96%

The dynamic relationship between inorganic polyphosphate and adenosine triphosphate in human non‐small cell lung cancer H1299 cells

Tsutsumi,

Tippayamontri,

Hayashi

et al. 2024

FEBS Open Bio

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Inorganic polyphosphate (polyP) plays a vital role in cellular energy metabolism and signaling, owing to its structure and high‐energy phosphate bonds. Intracellular ATP functions both as a cellular energy source and a key factor in cell death, and ATP dynamics in tumor cells are crucial for advancing cancer therapy. In this study, we explored the interplay between polyP and ATP in cellular energy metabolism. Treatment with polyP did not affect cell proliferation of human non‐small cell lung cancer H1299 and human glioblastoma T98G cell lines as compared to their respective control cells until 72 h post‐treatment. The mitochondrial membrane potential (MMP) in polyP‐treated cells was low, contrasting with the time‐dependent increase observed in control cells. While the ATP content increased over time in untreated and Na‐phosphate‐treated control cells, it remained unchanged in polyP‐treated cells. Furthermore, the addition of cyclosporine A, a mitochondrial permeability transition pore (mPTP) inhibitor, failed to restore ATP levels in polyP‐treated cells. We performed lactate assays and western blot analysis to evaluate the effect of polyP on glucose metabolism and found no significant differences in lactate secretion or glucose‐6‐phosphate dehydrogenase (G6PD) activity between polyP‐treated and control cells. Additional pyruvate restored MMP but had no effect on the cellular ATP content in polyP‐treated cells. We observed no correlation between the Warburg effect and glucose metabolism during ATP depletion in polyP‐treated cells. Further investigation is warranted to explore the roles of polyP and ATP in cancer cell energy metabolism, which might offer potential avenues for therapeutic interventions.

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Inorganic polyphosphate as an energy source in tumorigenesis

Cited by 10 publications

References 52 publications

Platelet polyphosphate and energy metabolism in professional male athletes (soccer players): A cross‐sectional pilot study

Platelet polyphosphate and energy metabolism in professional male athletes (soccer players): A cross‐sectional pilot study

Modulation of ATP Production Influences Inorganic Polyphosphate Levels in Non-Athletes’ Platelets at the Resting State

The dynamic relationship between inorganic polyphosphate and adenosine triphosphate in human non‐small cell lung cancer H1299 cells

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