Exploring the impact of a naturally occurring sapogenin diosgenin on underlying mechanisms of Ca²⁺ movement and cytotoxicity in human prostate cancer cells

Abstract

Literature has shown that diosgenin, a naturally occurring sapogenin, inducedcytotoxic effects in many cancer models. This study investigated the effect of diosgenin on intracellular Ca 2+ concentration ([Ca 2+ ]i) and cytotoxicity in PC3 human prostate cancer cells. Diosgenin (250-1000 μM) caused [Ca 2+ ]i rises which was reduced by Ca 2+ removal. Treatment with thapsigargin eliminated diosgenin-induced [Ca 2+ ]i increases. In contrast, incubation with diosgeninabolished thapsigargin-caused [Ca 2+ ]i increases. Suppression of phospholipase C with U73122 eliminated diosgenin-caused [Ca 2+ ]i increases. Diosgenin evoked Mn 2+ influx suggesting that diosgenin induced Ca 2+ entry. Diosgenininduced Ca 2+ influx was suppressed by PMA, GF109203X, and nifedipine, econazole, or SKF96365. Diosgenin (250-600 μM) concentration-dependently decreased cell viability. However, diosgenin-induced cytotoxicity was not reversed by chelation of cytosolic Ca 2+ with BAPTA/AM. Together, diosgenin evoked [Ca 2+ ]i increases via Ca 2+release and Ca 2+ influx, and caused Ca 2+ -non-associated deathin PC3 cells. These findings reveal a newtherapeutic potential of diosgenin for human prostate cancer.

Study on the Mechanism of Diosgenin Targeting STAT3 to Inhibit Colon Cancer Proliferation and Migration

“…For patients who have undergone radical surgeries or completed radiotherapy and chemotherapy, TCM treatment can also improve the body's immunity and inhibit tumor recurrence and metastasis. Recent studies have shown that the anticancer and cancer inhibitory theory of TCM mainly include antiangiogenesis, tumor cell proapoptosis, cytotoxicity, extracellular matrix antidegradation, improvement of body immunity, participation in regulation of cell signal transduction, and the attenuation and synergistic effect of radiotherapy and chemotherapy [ 24 , 25 ]. Chongqing Traditional Chinese Medicine Hospital is a special hospital of TCM.…”

“…Diosgenin increases the phosphorylation level of JNK to inhibit the proliferation of the breast cancer cells with a high expression of human epidermal growth factor receptor and to promote cell apoptosis, possibly by inhibiting Akt and mTOR phosphorylation [ 35 ]. Diosgenin inhibits the proliferation, migration, and invasion of PCa cell PC-3 in by suppressing the expression of VEGF and reducing the activity of matrix metalloproteinases [ 25 , 36 ]. In human chronic myelogenous leukemia K562 cells and HEL cell apoptosis studies, it has been found that G0/G1 cells are more prone to apoptosis, and diosgenin can increase the expressions of thromboxane synthase (TxS) and cyclooxygenase-2 and induce HEL cell differentiation [ 37 – 39 ].…”

Targeting autophagy in prostate cancer: preclinical and clinical evidence for therapeutic response

“…Diosgenin can promote NEDD4 E3 ubiquitin protein ligase Ca 2+ levels and flux. Furthermore, this compound causes Ca 2+ -independent cell death in prostate cancer cells [ 329 ]. Diosgenin administration significantly reduces proliferation and viability of prostate cancer cells via inducing autophagy.…”

Inhibition of invadopodia formation by diosgenin in tumor cells (Review)

“…Diosgenin was demonstrated to inhibit tumor growth in both MDA-231 and MCF-7 ×enografts in vivo by inhibiting Akt, the Raf/MEK signaling pathway and NF-κB activity to induce apoptosis ( 40 , 52 , 53 ). Therefore, diosgenin may be a potential option for the treatment of cancer ( 27 , 29 , 34 , 35 , 37 , 39 ).…”