Apigenin, a natural flavonoid, promotes autophagy and ferroptosis in human endometrial carcinoma Ishikawa cells in vitro and in vivo

Apigenin,a natural flavonoid has been reported against a variety of cancer types.However,it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells.There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells.We found that iron accumulation,lipid peroxidation,glutathione consumption,p62,HMOX1,and ferritin were increased,while,solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased.Ferrostatin-1,an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells.On the other hand,apigenin could promote autophagy via up-regulating Beclin 1,ULK1,ATG5,ATG13,and LC3B and down-regulating AMPK,mTOR,P70S6K,and ATG4.Furthermore,apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.

Regulatory Effect of Estrogen, Progestin and HB-EGF on the Expression of HOXA10 Gene in Ishikawa Cells

HOXA10 gene plays an essential role in differentiation of the endometrium and in human reproduction. The aim of this study was to investigate the regulatory effect of sex steroids and HB-EGF on HOXA10 gene in Ishikawa cells. Ishikawa cells were incubated with 17-beta estradiol （10-8 mol/L）, medroxyprogesterone acetate （MPA） （10^-6 tool/L）, RU486 （10^-5 mol/L） or HB-EGF （10 ng/mL） for 48 h respectively. The expression of HOXA10 gene was detected by immunofluorescence reverse transcriptase-polymerase chain reaction （RT-PCR） and Western blotting. Our results showed that either estrogen alone, progestin alone or progestin combined with estrogen could significantly increase the expression of HOXA10 gene 48 h after the treatment （P〈0.05）. But estrogen combined with progestin and RU486 could inhibit the up-regulation by estrogen and progestin. HB-EGF could elevate the expression of HOXA10 gene 48 h after the treatment （P〈0.05）. It is concluded that both estrogen and progestin can up-regulate the expression of HOXA10 gene in lshikawa cells, but RU486 can inhibit the effect and HB-EGF can elevate the expression level of HOXA10 gene.

Dioscin from Polygonatum sibiricum induces apoptosis and autophagy in Ishikawa human endometrial cancer cell and in vivo

With an aim to comprehend the precise regulatory mechanism of dioscin against endometrial carcinoma(EC), we firstly extracted the components from Polygonatum sibiricum followed by identification and structural characterization. The anti-EC activity of dioscin was initially determined based on the inhibition of Ishikawa cell proliferation and tumor growth. The high-throughput sequencing data indicated that dioscin not only promoted apoptosis, including decrease of poly ADP-ribose polymerase(PARP) and B-cell lymphoma-2(Bcl-2) and increase of c-PARP and Bcl-2-associcated agonist of cell death(Bad), but also induced autophagy, including increase of autophagic lysosomes and LC3Ⅱ/LC3Ⅰ ratio. Mechanistic exploration suggested that dioscin induced autophagy and apoptosis through inhibition of PI3K/AKT/mTOR signaling pathway. Besides, the dioscin-regulated p53 pathway was mainly involved in autophagy induction. Furthermore, inhibition of Ishikawa cell autophagy was linked to dioscin-induced apoptosis. Our data suggest the immense potential of dioscin for the development of functional food for EC and related medical application.