Table 3.

Pivotal findings of Mn²⁺ and Zn²⁺ roles in cancer physiology in vitro.

Main Finding	References
Mn2+-SOD2 drives H2O2 production in mitochondria in a wide range of extracellular concentrations	[6]
Mn2+ at high concentrations induces mitochondrial cell death	[72,151]
Zn2+ at high concentrations induces mitochondrial cell death	[13,74]
Zn2+ at low concentrations inhibits Mn-induced mitochondrial cell death	[73]
Low-molecular-weight complexes of Mn2+ predict cell survival, and double-strand breaks repair efficiency after gamma irradiation	[59]
Zn2+ release is required for and precedes ROS generation in mitochondria in response to hypoxia	[21,110]
Mn2+ activates p38/MSK1-regulated apoptosis	[72]
Zn2+ inhibits p38 and JNK and represses apoptosis in mutant G12V RAS cells	[147]
Zn2+ activates RAS signaling cascade	[146]
Mn2+ induces apoptosis or senescence by p53-dependent mechanisms	[151,152,153]
Zn2+ represses NF-κB activity and sensitizes prostate cancer cells to cytotoxic agents	[144,145,157]
Mn2+ represses histone acetylation by repressing HAT activity and augmenting HDAC, leading to apoptosis	[19]
Zn2+ activates HAT and MTF1-mediated transcription, leading to metallothionein induction and keratinocyte differentiation	[22]
Mn2+ is indispensable for cGAS-STNG activation and host defense against DNA viruses	[63]
Zn2+ coordination is required for cGAS–DNA liquid-phase condensation and cGAMP production	[172,173,174]