Phenethyl isothiocyanate sensitizes human cervical cancer cells to apoptosis induced by cisplatin

Abstract

Naturally-occurring chemopreventive agent phenethyl isothiocyanate (PEITC), derived primarily from watercress, has been shown to inhibit cell growth and induce apoptosis in cancer cells. In this study, we examined the potential of PEITC in enhancing cisplatin-induced apoptosis in cervical cancer cells. HeLa cells were exposed to PEITC, cisplatin or both. Pretreatment of cells with PEITC strongly enhanced cisplatin-induced cytotoxicity. PEITC activated the mitogen-activated protein kinases, including JNK, ERK, and p38. The synergistic induction of apoptosis was significantly attenuated by MEK1/2 inhibitor U0126, but not by JNK or p38 inhibitor, suggesting that ERK activation is responsible for the synergistic effect. We found that NF-κB signaling pathway is not involved in the synergistic effect. Sulforaphane and benzyl isothiocyanate, two other members of the isothiocyanate family, also sensitize HeLa cells to apoptosis induced by cisplatin. Furthermore, we found that the synergistic effect was not seen in normal cells. Finally, we demonstrated that Noxa induction was associated with apoptosis induced by PEITC plus cisplatin. Taken together, this study shows that PEITC can sensitize cancer cells to apoptosis induced by cisplatin and this effect is mediated through ERK activation, suggesting the potential of PEITC to be used as an adjuvant with cisplatin in combination therapeutic treatments.

ERK1/2 promoted proliferation and inhibited apoptosis of human cervical cancer cells and regulated the expression of c-Fos and c-Jun proteins

“…Specifically, U0126 reversed the EBPCmediated enhancement of cell death of cervical cancer, which is aldose reductase inhibitor that enhances the cytotoxic effects of the anticancer agent doxorubicin and cisplatin in Hela cervical cancer cells [19]. Similar study reported that U0126 blocked PEITC (a product of hydrolysis mediated by myrosinase) plus CDDP (an anticancer drug) induced apoptosis [20].…”

“…But, U0126, one of ERK1/2 inhibitors, has shown controversial effects on transformed cell lines proliferation for cervical cancer cells in vitro [19,20] and has not been researched in clinical development for any cancers.…”

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

“…This implies that sulforaphane enhances the efficiency of gemcitabine against the cancer cells, especially at lower doses, thereby minimizing its cytotoxicity to normal cells resulting in better survival. Other studies have also reported a synergistic interaction between different treatment strategies (Liu et al, 2001;Kuhar et al, 2007;Kumi-Diaka et al, 2010;Wang et al, 2011). Other studies of concurrent curcumin and chemotherapeutic drugs such as cisplatin, doxorubicin, and taxol showed that curcumin enhances the antitumor activities of the latter in various cancer cells (Chan et al, 2003;Notarbartolo et al, 2005).…”

The Anti-Cancer Effect of Watercress (Rorripa Nasturtium Aquaticum) Extract on Breast Cancer Cells

“…It is also denoted that PEI of watercress can prevent from cell growth through increasing Cisplatin which is one of the most important anticancer drugs used in the treatment of human tumors [14]. Furthermore, it is concluded that the PEI existing in watercress extract increases apoptosis as a result of inhibiting cyclooxygenase and angiogenesis in cancer cells.…”