TABLE 2.

Summarized mechanisms of non-apoptotic death of cancer cells following treatment with quercetin.

Cells/tumor	Quercetin concentration	Cell death type	Findings and involved mechanisms	References
T24 cellS	40, 60, or 80 μM	Senescence	Quercetin treatment showed an increase in the percentage of the nuclear characteristic of the senescence process, the cell nucleus area, as a result of the morphological analysis of the cell nuclei	Adami et al. (2021)
Colo-320 and Colo-741 cells	25 µM	Senescence	After treatment with quercetin, Lamin B1, p16, and cyclin B1 immunoreactivity were increased in Colo-320 and Colo-741 cells, which is usually considered a marker of cellular senescence	Özsoy et al. (2020)
C6 and U87 cells	25 μM	Senescence	Treatment with quercetin for four consecutive days increased the levels of senescence markers in C6 and U87 cells, furthermore senescence-associated cell morphological changes such as flattening, increased particle size, and cell enlargement could be observed. In addition, HDAC inhibited the positive effects of quercetin-induced senescence	Vargas et al. (2014)
U87-MG, U251 and SHG44 cells	50,100, or 200 μM	Senescence	Quercetin promotes glioma cell senescence via inhibition of the Ras/MAPK/ERK signaling pathway in a dose-dependent manner	Pan et al. (2015)
HeLa cells	30, 60, or 90 μM	Senescence	After 18 h of quercetin treatment, Hela cell density increased in the G2/M phase of the cell cycle, reflecting cell cycle arrest at that stage	Bishayee et al. (2013)
U251 cells	10, 20, 30, or 40 μM	Senescence	The number of U251 glioblastoma cells in sub-G2/M phase increased after treatment with quercetin (10–30 μM) for 24 h, indicating that quercetin caused G2/M phase arrest	Liu et al. (2017b)
SKOV3 and U2OSPt cells	10 and 50 µM	Senescence	After treatment with quercetin in SKOV3 and U2OSPt cells, cell cycle distribution was significantly altered. Quercetin treatment affected the cell cycle in G1/S and G2/M phases by decreasing cyclin D1 and cyclin B1 levels	Catanzaro et al. (2015)
A549 cells	10, 30, or 60 μM	Mitotic catastrophe	Quercetin treatment exerted the inhibitory effect on the proliferation of A549 cells mainly via the induction of mitotic catastrophe and apoptosis. The mechanism may involve the perturbation of mitotic microtubules, leading to the monopolar spindle formation, which leads to the failure of cytokinesis	(Klimaszewska-Wiśniewska et al., 2017)
Hepa1c1c7 cells	0.01 μM	Mitotic catastrophe	Low concentrations of quercetin treatment produced mitotic catastrophe. Disproportionate DNA segregation was observed when quercetin concentration was as low as 0.01 μM	Jackson et al. (2016)
MCF-7 and MDA-MB-231 cells	0.1, 1, and 10 μM	Ferroptosis	Quercetin treatment upregulated intracellular iron, carbonyl protein, and MDA levels in breast cancer cells in a dose-dependent manner. The pharmacological effects of quercetin on killing breast cancer cells might be related to the promotion of TFEB expression and nuclear transcription, which induce the occurrence of iron death	An and Hu, (2022)
HepG2, Hep3B, MDA-MB- 231, and HCT116 cells	50 μM	Ferroptosis	Quercetin possesses the effect of promoting lysosome-dependent ferritin degradation and free iron release, which in synergy with quercetin-induced ROS generation leads to lipid peroxidation and ferroptosis.	Wang et al. (2021a)
MCF-7 cells	50 μM	Necroptosis	Quercetin significantly inhibited MCF-7 cell viability and proliferation via activation of apoptotic and necroptosis signaling pathways. Quercetin possesses a necroptosis-inducing effect possibly by increasing the expression of RIPK1 and RIPK3	Khorsandi et al. (2017)
Giant cell tumor of bone	120 μM	Necroptosis and autophagy	The ultrastructural changes observed in giant cell tumors of bone cultured quercetin for 24 h corresponded mainly to necroptosis, secondary necrosis, and autophagocytosis	Estrada-Villaseñor et al. (2021)
4T1 cells nude mice with subcutaneous injection of 4T1 cells (107/mL)	Not mentioned (in vivo) 20 mg/kg/day, i.p. (in vivo)	Pyroptosis	Quercetin-treated BCRD rat, serum IFN-γ, IL-10, and IL- 2 levels were significantly upregulated, which probably via promoting anti-tumor immune response. In addition, quercetin partially reversed the pyroptosis on LPS-cultured 4T1 cells in vitro, as evidenced markedly by upregulating the ASC, NLRP3 and Caspase-1	Zhu et al. (2022)