Induction of Apoptosis in HeLa Cells via Caspase Activation by Resveratrol and Genistein

Abstract

Selectively inducing apoptosis in cancer cells is a much desired strategy when tolerance toward side effects is minimal during chemotherapy. In our search for natural products that can induce apoptosis in human cervical cancer cells (HeLa), we selected resveratrol and genistein for our study. We conducted several experiments to test whether genistein can synergistically enhance the apoptotic potential of resveratrol at doses lower than the usual cytotoxic dose. Both resveratrol and genistein were able to induce apoptosis by enhancing the activities of caspase-9 and caspase-3 by themselves and also in combination. After 24 h of exposure to resveratrol and genistein, individually or in combination, lowered mitochondrial membrane potential was observed in HeLa cells. In addition, the mitochondrial membrane potential in HeLa cells was decreased, forcing JC-1 to stay in the monomeric form. The monomeric JC-1(5,5',6,6' -tetrachloro-1,1',3,3'-tetraethyl benzimedazolyl carbocyanine iodide) emitted green fluorescence. In the control group, the color of the fluorescence was red due to aggregation of JC-1 in the physiological pH. The treatment groups exhibited DNA fragmentation as the hallmark of apoptotic nuclear features. We also detected an obvious decrease in the level of HDM2 gene expression after both individual and combination treatments with resveratrol and genistein. Our findings suggest that resveratrol and genistein when combined can induce apoptosis at doses lower than usual doses, through the activation of caspases cascade, and by decreasing the expression of HDM2.

Genistein inhibits the growth and regulates the migration and invasion abilities of melanoma cells via the FAK/paxillin and MAPK pathways

“…Furthermore, genistein induced its apoptotic effect in a dose-dependent manner. This observation is in agreement with the cytotoxic properties of genistein reported in other studies using different cell types [40, 43, 44]. …”

“…Genistein has been reported to suppress tumor cell growth and induce apoptosis in several tumor cell lines through different molecular pathways, including cell cycle arrest, mitochondria-dependent pathways, MAPK pathways, and caspase-dependent pathways [38–43]. However, little is currently known about genistein's effects on melanoma cells, especially its anti-metastatic potential on the FAK/paxillin pathway.…”

A comprehensive anticancer molecular study for genistein the promising anticancer drug

“…11,12 Furthermore, genistein, an isoflavone finds in many plants especially soybeans and fava beans proved to be highly effective anticancer compound. 2,3,6 The results of this study have clarified the real anticancer mechanism of this highly promising anticancer drug, Genistein anticancer molecular mechanism Original Rand R. Hafidh genistein. Also, the massive cancer genomic data of genistein anticancer activity were searched to facilitate the development of molecularly targeted cancer therapies.…”

“…Hence, genistein is able to lower mortality linked to solid organ cancer by important mechanisms. 3,6 The ability to reduce the mortality associated with various cancer types, particularly cervical cancer is because this vital small molecule has a moderately extensive array of biological activities.…”

Genistein Increase Intracellular Distribution of the High Motility Group Box-1 through p38 Pathway in HeLa culture cells induced by Tumor Necrosis Factor-α

“…This made clear by other studies stating that p38 is one of the apoptosis cell intermediate [32,33]. It explains increasing in the intensity of p38 at dose 50 µM, where this dose as indicated on Szliszka, et al, 2008 is apoptotic dose of genistein [34].…”