Role of Pd(II)-chitooligosaccharides-Gboxin analog in oxidative phosphorylation inhibition and energy depletion: Targeting mitochondrial dynamics.

In this work, we have successfully upgraded the crab wastes into Pd(II) complex of Gboxin analog-chitooligosaccharides conjugate (Pd(II)COS@GbA). This new complex has a high capacity to inhibit the proliferation of prostate cancer cells (IC50  = 1.92 μg/ml). This activity could be attributed to its ability to induce mitochondrial fragmentation through increasing mitochondrial fission dynamin-related protein 1 (p < .05) and down-regulation of optic atrophy 1 proteins (p < .05). Moreover, this complex can effectively disrupt ATP synthase action leading to declined ATP production, along with downstream of ATPase inhibitor factor1 that hinder energy production in the cancer cells. Also, it has an anti-inflammatory effect by triggering modulators for the release of inflammatory molecules such as TNF-α (p < .05), IL-6 (p < .05), and mRNA transcripts of COX-II (p < .01). Therefore, Pd(II)COS@GbA exhibited significant anti-prostate cancer activity through different mechanisms in inducing energy depletion and mitochondrial fragmentation leading to disrupted oxidative phosphorylation (OXPHOS). Complex Pd(II)COS@GbA is more cytotoxic for PC3 than RWPE-1 which in turn means it is may act as a selective cytotoxic agent for prostate cancer.