Isothiocyanates sensitize the effect of chemotherapeutic drugs via modulation of protein kinase C and telomerase in cervical cancer cells

Abstract

Isothiocyanates have potential chemopreventive and antitumor effects. In the present study, we examined the actions of PEITC and sulphoraphane in modulating the activity of protein kinase C (PKC) and telomerase in cervical cancer cell line HeLa. These tumor markers are highly activated in human cancers. These compound efficiently downregulated the antiapoptotic isoforms (PKC-alpha, -betaII, -epsilon, and -zeta) as well as telomerase, whereas the proapoptotic form (PKC-delta) was upregulated. Studies were performed to measure the degree of apoptotic cell death induced by either isothiocyanates alone, or in combination with adriamycin or etoposide. Apoptosis was evident from mitochondrial cytochrome c release, apoptotic index and caspases 3 and 8 activation. Results showed that pretreatment exhibited better efficacy in sensitizing HeLa cells toward apoptosis by modulating PKCs, telomerase. This effect of isothiocyanates might prove to be of considerable value in synergistic therapy of cancer such that the drug dose level could be minimized.

Molecular Cloning and Expression Analysis of COX II from <em>Sitophilus zeamais</em>, a Potential Action Site of AITC

“…In recent years, a number of mechanisms have been proposed for the activities of AITC [25][26][27][28][29][30][31][32][33], such as microtubule, proteasome, nucleus, mitochondria, ABC transportes and TPR channel. However, identifying the molecular targets is a first step to make sure the molecular mechanisms of AITC.…”

Mechanisms of the Anticancer Effects of Isothiocyanates

“…The combination of metformin and PEITC showed high efficacy in cisplatin resistant cancer cells [145]. PEITC and SFN enhanced the apoptotic effects of Adriamycin and etoposide by inhibition of protein kinase C [146]. SFN also increased the susceptibility of Adriamycin to resistant cells [144].…”

Phenethyl isothiocyanate: A comprehensive review of anti-cancer mechanisms

“…Often, cancer cells exploit telomerase enzyme to alter the length of telomeres rendering them immortal [128]. PEITC has been shown to inhibit telomerase activity in prostate and cervical cancer cells [129, 130]. Furthermore, it was observed that pre-treatment with PEITC induced apoptosis as well as increased the efficacy of adriyamycin and etoposide by inhibiting protein kinase C and telomerase [130].…”