Histone Potentiates Inositol Hexakisphosphate in Inducing Apoptosis of HONE-1 Nasopharyngeal Cancer Cells

Sandra, Ferry; Rahayu, Wiryadani; Anthony, Ian; Lokantari, Miranti Anggorodhiyu; Annisa, Sheila; Chouw, Angliana; Celinna, Maria; Lee, Kyung Hoon

doi:10.1590/1678-4324-2025240110

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Article - Human and Animal Health • Braz. arch. biol. technol. 68 • 2025 • https://doi.org/10.1590/1678-4324-2025240110 linkcopy

Histone Potentiates Inositol Hexakisphosphate in Inducing Apoptosis of HONE-1 Nasopharyngeal Cancer Cells

Authorship SCIMAGO INSTITUTIONS RANKINGS

Inositol hexakisphosphate (InsP₆) requires relatively high concentrations to induce apoptosis of cancer cells, which can possibly cause apoptosis of normal cells. Anticancer ability of InsP₆ could be preserved by combining with histone, so InsP₆ can be used at low concentrations. The effect of InsP₆ and histone combination has not been investigated on nasopharyngeal cancer cells. The current study elucidated the effect of InsP₆ and its combination with histone on the apoptosis of HONE-1 cells. The most effective concentration and the cellular mechanisms by which this combination exerts its anticancer effects were also investigated. HONE-1 and NIH3T3 cells (as normal control cells) were treated with InsP₆ and/or histone in different concentrations. Apoptosis percentages of the treated cells were measured with sub-G1 assay. Nuclear fragmentation and mitochondrial membrane potential (∆Ψm) reduction in the treated HONE-1 cells were confirmed with 4',6-diamidino-2-phenylindole (DAPI) staining and ∆Ψm assay, respectively. The combination of 10 μM InsP₆ and 10 μg/mL histone had the optimal ability to induce the apoptosis of HONE-1 cells. This combination did not induce apoptosis of NIH3T3 cells. The apoptosis-inducing ability of this combination was higher than that of 10 μM InsP₆ merely. The ability of InsP₆ to induce apoptosis of HONE-1 cells could be enhanced by histone application. Combination of 10 μM InsP₆ and 10 μg/mL histone might be the optimal concentrations for inducing apoptosis in HONE-1 cells.

Keywords:
inositol hexakisphosphate; histone; apoptosis; HONE-1 cells.

InsP₆ has the ability to induce apoptosis in HONE-1 nasopharyngeal cancer cells.

Apoptosis-inducing ability of InsP₆ can be enhanced by histone application.

Combination of InsP₆ and histone decreases ∆Ψm in HONE-1 cells.

Combination of InsP₆ and histone induces nuclear fragmentation in HONE-1 cells.

Treatment	Untreated	H₂O₂	InsP₆ (μM)				Histone (μg/mL)				10 μM InsP₆ + Histone (μg/mL)				100 μM InsP₆ + Histone (μg/mL)
Treatment	Untreated	H₂O₂	1	10	100	500	1	10	100	500	1	10	100	500	1	10	100	500
Untreated	-	*	NS	NS	*	*	NS	NS	NS	NS	NS	NS	NS	NS	*	*	*	*
H₂O₂	*	-	*	*	*	*	*	*	*	*	*	*	*	*	*	*	*	*
1 μM InsP₆	NS	*	-	NS	*	*	NS	NS	NS	NS	NS	NS	NS	NS	*	*	*	*
10 μM InsP₆	NS	*	NS	-	*	*	NS	NS	NS	NS	NS	NS	NS	NS	*	*	*	*
100 μM InsP₆	*	*	*	*	-	*	*	*	*	*	*	*	*	*	NS	*	*	*
500 μM InsP₆	*	*	*	*	*	-	*	*	*	*	*	*	*	*	*	*	NS	NS
1 μg/mL histone	NS	*	NS	NS	*	*	-	NS	NS	NS	NS	NS	NS	NS	*	*	*	*
10 μg/mL histone	NS	*	NS	NS	*	*	NS	-	NS	NS	NS	NS	NS	NS	*	*	*	*
100 μg/mL histone	NS	*	NS	NS	*	*	NS	NS	-	NS	NS	NS	NS	NS	*	*	*	*
500 μg/mL histone	NS	*	NS	NS	*	*	NS	NS	NS	-	NS	NS	NS	NS	*	*	*	*
10 μM InsP₆ + 1 μg/mL histone	NS	*	NS	NS	*	*	NS	NS	NS	NS	-	NS	NS	NS	*	*	*	*
10 μM InsP₆ + 10 μg/mL histone	NS	*	NS	NS	*	*	NS	NS	NS	NS	NS	-	NS	NS	*	*	*	*
10 μM InsP₆ + 100 μg/mL histone	NS	*	NS	NS	*	*	NS	NS	NS	NS	NS	NS	-	NS	*	*	*	*
10 μM InsP₆ + 500 μg/mL histone	NS	*	NS	NS	*	*	NS	NS	NS	NS	NS	NS	NS	-	*	*	*	*
100 μM InsP₆ + 1 μg/mL histone	*	*	*	*	NS	*	*	*	*	*	*	*	*	*	-	*	*	*
100 μM InsP₆ + 10 μg/mL histone	*	*	*	*	*	*	*	*	*	*	*	*	*	*	*	-	*	*
100 μM InsP₆ + 100 μg/mL histone	*	*	*	*	*	NS	*	*	*	*	*	*	*	*	*	*	-	NS
100 μM InsP₆ + 500 μg/mL histone	*	*	*	*	*	NS	*	*	*	*	*	*	*	*	*	*	NS	-

Treatment	Untreated	TRAIL	InsP₆ (μM)			Histone (μg/mL)				10 μM InsP₆ + Histone (μg/mL)				100 μM InsP₆ + Histone (μg/mL)
Treatment	Untreated	TRAIL	1	10	100	1	10	100	500	1	10	100	500	1	10
Untreated	-	*	NS	*	*	NS	NS	NS	NS	*	*	*	*	*	*
TRAIL	*	-	*	*	*	*	*	*	*	*	*	*	*	*	*
1 μM InsP₆	NS	*	-	*	*	NS	NS	NS	NS	*	*	*	*	*	*
10 μM InsP₆	*	*	*	-	*	*	*	*	*	NS	*	*	*	*	*
100 μM InsP₆	*	*	*	*	-	*	*	*	*	*	*	*	*	NS	*
1 μg/mL histone	NS	*	NS	*	*	-	NS	NS	NS	*	*	*	*	*	*
10 μg/mL histone	NS	*	NS	*	*	NS	-	NS	NS	*	*	*	*	*	*
100 μg/mL histone	NS	*	NS	*	*	NS	NS	-	NS	*	*	*	*	*	*
500 μg/mL histone	NS	*	NS	*	*	NS	NS	NS	-	*	*	*	*	*	*
10 μM InsP₆ + 1 μg/mL histone	*	*	*	NS	*	*	*	*	*	-	*	*	*	*	*
10 μM InsP₆ + 10 μg/mL histone	*	*	*	*	*	*	*	*	*	*	-	NS	NS	*	NS
10 μM InsP₆ + 100 μg/mL histone	*	*	*	*	*	*	*	*	*	*	NS	-	NS	*	NS
10 μM InsP₆ + 500 μg/mL histone	*	*	*	*	*	*	*	*	*	*	NS	NS	-	*	NS
100 μM InsP₆ + 1 μg/mL histone	*	*	*	*	NS	*	*	*	*	*	*	*	*	-	*
100 μM InsP₆ + 10 μg/mL histone	*	*	*	*	*	*	*	*	*	*	NS	NS	NS	*	-

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[1] NS = not significant;

[TFN1] ^*
significant with p<0.05.Histone did not induce apoptosis of NIH3T3 cells at concentration of 1-500 μg/mL, as indicated by the apoptosis percentages that were not significantly different when compared with that of untreated NIH3T3 cells. The combination of 1-500 μg/mL histone + 10 μM InsP₆ also did not induce apoptosis of NIH3T3 cells (Figure 1, Table 1). However, when 1-500 μg/mL histone was combined with 100 InsP₆, apoptosis percentages of NIH3T3 cells were significantly higher as compared with combination of 1-500 μg/mL histone + 10 μM InsP₆ (p<0.05, Mann-Whitney test) (Table 1).