Protein kinase Cα-mediated cytotoxic activity of ineupatorolide B from Inula cappa DC. in HeLa cells

Abstract

There is an ongoing search for plant-derived sesquiterpenes, particularly for those with anticancer activity against human cancer cells. The sesquiterpene ineupatorolide B (InB), isolated from the Inula cappa, showed potent growth-inhibitory activity against HeLa cells but less activity against MM1-CB melanoma cells. Staining by terminal deoxynucleotidyl transferase dUTP nick-end labeling method revealed that this activity was, at least in part, due to the induction of apoptosis. The activities of major transcription factors were examined by using a luciferase reporter assay. The results showed that the transactivation ability of nuclear factor of activated T-cell (NFAT) was enhanced. The activation of NFAT by InB was largely suppressed by preincubation with protein kinase C (PKC) inhibitors such as staurosporine and K252a. Western blot analysis revealed that the the levels of phosphorylated PKCα, but not other subtypes, increased after treatment with InB. Knockdown of PKCα using siRNA attenuated the cytotoxic activity of InB. Thus, InB may exhibit growth-inhibitory activity through the activation of PKCα, followed by an increase in NFAT transactivation ability.

Comparative pharmacokinetic study of the five anti-inflammatory active ingredients of Inula cappa in a normal and an LPS-induced inflammatory cell model

“…I. cappa is mainly composed of terpenoids, flavonoids, phenols, organic acids, and volatile oil ( Xie, et al, 2007 ; Yao and Liang, 2008 ; Wu, et al, 2010 ; Hu and He, 2012 ; Guan, et al, 2014 ; Wu, et al, 2017 ; Yao, 2017 ; Zhou, et al, 2017 ). Modern pharmacological studies have indicated that I. cappa has many biological activities and exerts anti-inflammatory, analgesic, antibacterial, antitumor, antioxidant, and immunomodulatory effects ( Liu et al, 2009 ; Liu, et al, 2010 ; Jiraporn, et al, 2011 ; Xie, et al, 2012 ; Dong, et al, 2015 ; Li, 2017 ). Compared with the many studies on the pharmacological properties and chemical composition of I. cappa , there are few pharmacokinetic studies on its active ingredients, and cellular pharmacokinetic studies on its active ingredients are still lacking.…”

Millifolide A, a dimeric ether of degraded sesquiterpene lactones, inhibited the proliferation of human lung cancer cell line A549

“…Yarrow (Achillea millefolium L.) as the composite yarrow perennial herbaceous plants in the family Asteraceae, is used as a folk medicine for the treatment of injuries, amenorrhea abdominal pain, rheumatic pain, snake bites, carbuncle furuncle swollen poison etc. Traditional Chinese medicine theory believes that this bitter medicine has the function of clearing heat and toxin, promoting blood flow for regulating menstruation (Dong et al 2015). We have come to the idea that the variety of medicinal activities of yarrow plants are attributed to the sesquiterpene lactones with an exo-a,b-unsaturated double bond act as a strong Michael acceptor.…”