Clove Extract Inhibits Tumor Growth and Promotes Cell Cycle Arrest and Apoptosis

Abstract

Cloves (Syzygium aromaticum) have been used as a traditional Chinese medicinal herb for thousands of years. Cloves possess antiseptic, antibacterial, antifungal, and antiviral properties, but their potential anticancer activity remains unknown. In this study, we investigated the in vitro and in vivo antitumor effects and biological mechanisms of ethyl acetate extract of cloves (EAEC) and the potential bioactive components responsible for its antitumor activity. The effects of EAEC on cell growth, cell cycle distribution, and apoptosis were investigated using human cancer cell lines. The molecular changes associated with the effects of EAEC were analyzed by Western blot and (qRT)-PCR analysis. The in vivo effect of EAEC and its bioactive component was investigated using the HT-29 tumor xenograft model. We identified oleanolic acid (OA) as one of the components of EAEC responsible for its antitumor activity. Both EAEC and OA display cytotoxicity against several human cancer cell lines. Interestingly, EAEC was superior to OA and the chemotherapeutic agent 5-fluorouracil at suppressing growth of colon tumor xenografts. EAEC promoted G0/G1 cell cycle arrest and induced apoptosis in a dose-dependent manner. Treatment with EAEC and OA selectively increased protein expression of p21WAF1/Cip1 and γ-H2AX and downregulated expression of cell cycle-regulated proteins. Moreover, many of these changes were at the mRNA level, suggesting transcriptional regulation by EAEC treatment. Our results demonstrate that clove extract may represent a novel therapeutic herb for the treatment of colorectal cancer, and OA appears to be one of the bioactive components.

Upregulation of nuclear factor‐κB activity mediates CYP24 expression and reactive oxygen species production in indoxyl sulfate‐induced chronic kidney disease

“…Total RNA was extracted from the cells or tissues by Trizol Reagent (Invitrogen, Carlsbad, CA, USA). qRT‐PCR was performed as described previously . The relative expression ratio of mRNA was calculated by the 2 −ΔΔCT method.…”

Aqueous extract of clove inhibits tumor growth by inducing autophagy through AMPK/ULK pathway

“…Cloves ( Syzygium aromaticum ), a traditional Chinese medicinal herb, contains a wide range of bioactive compounds, including eugenol, β‐caryophyllene, and eugenone, flavonoids eugenin, and oleanolic acid (Cortes‐Rojas, Fernandes de Souza, & Oliveira, ). Our previous study has confirmed that the ethyl acetate extract of cloves (EAEC) can inhibit tumor growth and induce apoptosis in colorectal cancer cell HT‐29 (Liu et al, ). During screening program for identifying potential antitumor agents from cloves, we found that the aqueous extract of cloves (AEC) displayed more potent antitumor activity.…”

“…Our previous study showed that the EAEC contains two main components, eugenol and oleanic acid, responsible for its anticancer activity (Liu et al, ). However, the result of LC–MS analysis shows that the eugenol and oleanic acid were not involved in the fraction of AEC whereas nine components have been identified including chlorogenic acid, isochlorgenic acid, quercetin‐3‐O‐β‐D‐glucuronide, kaempferol 3‐O‐β‐glucuronide, isorhamnetin‐3‐O‐β‐D‐glucoside, isorhamnetin‐3‐O‐β‐D‐glucuronide, rhamnetin‐3‐O‐β‐D‐glucuronide, rhamnazin‐3‐O‐β‐D‐glucoside, and rhamnazin‐3‐O‐β‐D‐glucuronide.…”

Development of Certain Protein Kinase Inhibitors with the Components from Traditional Chinese Medicine

“…Our recent study revealed that the crude extract of clove bud can induce cell death via apoptotic pathway and inhibit the growth of cancer cells both in vitro and in vivo . However, the isolated bioactive component, Oleanolic acid, displays much weaker antitumor activity compared to the crude extract in the nude mouse models of xenografted human tumors, suggesting synergistic antitumor effects exist among the components in the extract of clove bud (Liu et al, 2014). …”