Concurrent Sulforaphane and Eugenol Induces Differential Effects on Human Cervical Cancer Cells

Abstract

Background. The concept of combination of chemoprevention holds great potential for cancer management as lower, clinically tolerable doses of individual agents could be achieved through therapeutic synergy. However, elucidation of their possible interactions-additive, synergistic, or antagonistic-must be thoroughly studied before considering for clinical use. Methods. To evaluate the effect of combination treatment of sulforaphane (SFN) and eugenol on HeLa cells, the authors performed cell viability assay, apoptosis assay, and reverse transcription polymerase chain reaction for gene expression analysis. Calculations of combination effects were expressed as a combination index (CI) with CI < 1, CI = 1, or CI > 1 representing synergism, additivity, or antagonism, respectively. Results. Simultaneous treatment with variable dose combinations of SFN and eugenol resulted in differential effects with an antagonistic effect at lower and synergistic at higher sub-lethal doses as reflected in cell cytotoxicity and apoptosis induction. Importantly, gemcitabine used in conjunction with the low-and high-dose combinations showed no significant cell death at lower doses suggesting that cell cytotoxicity is proportional to gemcitabine alone, whereas at higher sublethal doses of SFN and eugenol, it was found to act in a synergistic manner with gemcitabine. Furthermore, SFN and eugenol combinations at synergistic dose significantly downregulated the expression of Bcl-2, COX-2 and IL-β but not the antagonistic combinations. Conclusion. This study clearly indicates that 2 (or more) chemopreventive agents can act antagonistically or synergistically necessitating elucidation of possible mechanistic interactions for favorable and reliable outcomes of dietary components in the field of cancer prevention.

A black raspberry extract inhibits proliferation and regulates apoptosis in cervical cancer cells

“…The alkaloid compound (−)-anonaine derived from Michelia alba trees [26], the isothiocyanate sulforaphane (SFN) [27], and the combination of SFN with eugenol [28] have all been reported to induce apoptosis in HPV18 + HeLa cervical cancer cells. Similarly, an aqueous extract from the bark of Cinnamomum cassia promoted apoptosis in HPV16 + SiHa human cervical cancer cells [29].…”

Anticancer Activities of Essential Oils Constituents and Synergy with Conventional Therapies: A Review

“…Among aromatic EO constituents, eugenol is one of the most active and then most studied. Eugenol induces apoptosis of cervical cancer cells without toxicity to healthy cells and potentiates the effect of chemotherapeutic agents: gemcitabine (Hussain et al , ) or sulforaphane (Hussain et al , ).…”

Sulforaphane induced cell cycle arrest in the G2/M phase via the blockade of cyclin B1/CDC2 in human ovarian cancer cells

“…SFN is also a potent scavenger of reactive oxygen species (ROS), including superoxide anions and hydroxyl radicals [7]. Many studies have indicated an inverse correlation between the consumption of cruciferous vegetables and a decrease in the incidence of various tumors, including those of the prostate [8], cervical [9], colorectal [10], and lung [11]. In addition to inhibiting cell proliferation and increasing apoptosis [10], other mechanisms have also been proposed to explain the anti-carcinogenic effects of SFN.…”