Tellimagrandin I enhances gap junctional communication and attenuates the tumor phenotype of human cervical carcinoma HeLa cells in vitro.
Tellimagrandin I and chebulinic acid, two hydrolysable tannins, have been shown to exert anti-tumor properties. Dysfunctional gap junctional communication (GJIC) has been recognized as being involved in carcinogenesis. The human cervical carcinoma HeLa cells have been reported to be deficient in functional GJIC. In present study, we investigated whether tellimagrandin I and chebulinic acid might restore functional GJIC in HeLa cells. Both compounds could inhibit the growth of HeLa cells. Either Lucifer yellow transfer assay or calcein transfer assay demonstrated that tellimagrandin I improved GJIC in HeLa cells while chebulinic acid showed no effect on GJIC. The GJIC enhancement by tellimagrandin I occurred along with an increase of Cx43 gene expression at mRNA and protein levels. Exposure to tellimagrandin I also led to inhibition of proliferation and anchorage-independent growth of HeLa cells. In addition, tellimagrandin I decreased the percentage of cells in the G0/G1 and G2/M phases coinciding with an increase in the percentage of cells in the S phase. The accumulation of cells in S phase was coupled with a decreased expression of cyclin A that was critical to the progression of S phase. These results suggested that restoring GJIC might be one explanation for tellimagrandin I antitumor effects, whereas chebulinic acid exerted antitumor action through other pathways.
Yi
Zong-Chun
ZC
Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, China. yizc@buaa.edu.cn
Liu
Yan-Ze
YZ
Li
Hai-Xia
HX
Yin
Yan
Y
Zhuang
Feng-Yuan
FY
Fan
Yu-Bo
YB
Wang
Zhao
Z
D000970:Antineoplastic Agents / Q000494:pharmacology; D018031:Connexin 43 / Q000096:biosynthesis; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D005260:Female; D005452:Fluoresceins / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017629:Gap Junctions; D015972:Gene Expression Regulation, Neoplastic; D005960:Glucosides / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D047348:Hydrolyzable Tannins / Q000494:pharmacology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D010641:Phenotype; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology*
D000970:Antineoplastic Agents; D018031:Connexin 43; D004365:Drugs, Chinese Herbal; D005452:Fluoresceins; D005960:Glucosides; D047348:Hydrolyzable Tannins; D007546:Isoquinolines; C103481:chebulinic acid; D005707:Gallic Acid; C087926:tellimagrandin I; C017475:lucifer yellow; C007740:fluorexon