Abstract
In Taoism, all entities in the universe embody two complementary forces—Yin and Yang—that are oppositional yet unified. Their subtle interplay governs the direction and progression of events. Caspase-3 is renowned for mediating apoptosis, whereas accumulating evidence has revealed its role in stimulating compensatory proliferation. In cancer, while caspase-3 activation is traditionally regarded as tumor-suppressive due to its ability to induce cell death, particularly apoptosis, increasing evidence has highlighted its tumor-supportive functions. These dual roles of caspase-3 exemplify the Taoist principle of “Yin and Yang”. This review begins by outlining the canonical apoptotic role of caspase-3, and then discusses its non-apoptotic roles across diverse pathophysiological contexts, with specific emphasis on its tumor-supportive mechanisms in: tumor repopulation, tumor angiogenesis, tumorigenesis, tumor migration, invasion and metastasis, cancer stem cell maintenance, therapy resistance, and tumor immune response. The emerging tumor-promoting functions of caspase-3 challenge the conventional therapeutic paradigm of activating caspase-3. Instead, caspase-3 inhibition may represent a promising alternative strategy for cancer treatment.