Inducers of Senescence, Toxic Compounds, and Senolytics: The Multiple Faces of Nrf2-Activating Phytochemicals in Cancer Adjuvant Therapy

Table 1

Estimated IC₅₀ for senescent and nonsenescent cells of natural bioactive compounds with reported senolytic activity observed in vitro after the exposure time reported in brackets.

IC50

Senescent cells

Nonsenescent cells

Reference

Compound

IRS IMR-90

IRS WI-38

RIS WI-38

OIS WI-38

IRS HUVEC

IRS ADP

TIS LYMP

IMR-90

WI-38

HUVEC

ADP

LYMP

Fisetin

50 μM (72 h)

30 μM (72 h)

>>60 μM (72 h)

>50 μM (72 h)

>60 μM (72 h)

>>60 μM (72 h)

[44]

Quercetin

10 μM (72 h)

>50 μM (72 h)

30 μM (72 h)

>50 μM (72 h)

[38]

Piperlongumine

7.97 μM (72 h)

6.24 μM (72 h)

7.09 μM (72 h)

20.3 μM (72 h)

[46]

Phloretin

50 μM^#(120 h)

>>50 μM^# (120 h)

[45]

The highest concentration tested in the respective reference (IC₅₀ not measured); IRS = irradiation-induced senescence; OIS = oncogene-induced senescence; RIS = replicative-induced senescence; ADP = preadipocytes; LYMP = lymphoma; ^#unique dose studied. The IC₅₀ highlighted in bold are those supporting a senolytic activity (based on the difference with nonsenescent cells).