Chemosensitizing Effect of Cernumidine Extracted from Solanum cernuum on Bladder Cancer Cells in Vitro

Abstract

Cernumidine (CER) is a guanidinic alkaloid isolated from Solanum cernuum leaves. In this work, we investigated the cytotoxicity, chemosensitizing effect of cernumidine to cisplatin (cDDP) and the possible mechanism of action of the combination on bladder cancer cells. Cernumidine showed cytotoxicity and could sensitize bladder cancer cells to cisplatin. The combination of CER+cDDP inhibited cell migration on T24 cells. CER+cDDP down‐regulated MMP‐2/9 and p‐ERK1/2, while it increased EGFR activity corroborating the observed cell migration inhibition. Down‐regulation of Bcl‐2 and up‐regulation pro‐apoptotic Bax and further depletion of the mitochondrial membrane potential (ΔΨm) indicates that mitochondria play a central role in the combination treatment inducing the mitochondrial signaling pathway of apoptosis in T24 cells. Our data showed that the alkaloid cernumidine is worthy of further studies as a chemosensitizing agent to be used in complementary chemotherapy.

Remedying the Mitochondria to Cure Human Diseases by Natural Products

“…With the deepening of research, it is believed that more natural products that can regulate the mitochondria have the potential to be used in treating diseases, which is of utmost importance. Oxidative Medicine and Cellular Longevity [44] Oxidative stress Bulbine frutescens [37] Bullfrog oil [38] Orientin [40] Asparanin A [42] Gracillin [44] Apoptosis Bulbine frutescens [37] Orientin [40] Licochalcone A [41] Asparanin A [42] Parameritannin A-2 [43] Cernumidine [45] Mitochondrial membrane potential imbalance Bullfrog oil [38] Rhein [39] Asparanin A [42] Cernumidine [45] Neurodegenerative diseases…”

Matrix Metalloproteinases in Chemoresistance: Regulatory Roles, Molecular Interactions, and Potential Inhibitors

“…Two other studies conducted by Yao et al [ 168 , 169 ] utilized MMP-2 cleavable pp linkers for targeted drug delivery. In one study, they developed a dual-targeting micelle that is activated by MMP-2 and bound to folate receptors (FR) on the cell surface [ 168 ].…”

“…Two other studies conducted by Yao et al [ 168 , 169 ] utilized MMP-2 cleavable pp linkers for targeted drug delivery. In one study, they developed a dual-targeting micelle that is activated by MMP-2 and bound to folate receptors (FR) on the cell surface [ 168 ]. The MMP/FR micelle inhibited Pgp-mediated drug efflux on MMP-2 expressing and FR expressing ovarian NCI/ADR-RES cells and breast MDA-MB-231 cells.…”

Natural Products Targeting the Mitochondria in Cancers

“…Natural products of the APD-class have hypoxiaactivated cytotoxins, targeting mitochondria [103]. Cernumidine ( 50) is a guanidinic alkaloid, which exerted antitumor effects through mitochondria by downregulating the Bcl-2/Bax ratio and causing MMP loss in the combination treatment with cisplatin in T24 cells [104]. Lycorine (51), extracted from plants of the Amaryllidaceae family, induced apoptosis in HepG2 cells through mPTP opening, ATP depletion, MMP loss, and mitochondrial Ca 2+ and cytochrome c release [105].…”