title: Deoxyrhapontigenin, a Natural Stilbene Derivative Isolated From Rheum undulatum L. Induces Endoplasmic Reticulum Stress-Mediated Apoptosis in Human Breast Cancer Cells.
abstract: Although current chemotherapeutic agents are active at the beginning of therapy, the most common risk is the development of resistance during later stages in almost all cancer types including breast cancer. Hence, investigation of novel drugs is still a priority goal for cancer treatment. The objective of the present study is to investigate the anticancer effect of a derivative of stilbene, deoxyrhapontigenin (DR) isolated from Rheum undulatum L. root extracts against the chemoresistant MCF-7/adr and its parental MCF-7 human breast cancer cells. The morphological images indicate that DR induces an extensive cytoplasmic vacuolation in breast cancer cells. Mechanistic investigations revealed that DR treatment causes endoplasmic reticulum (ER) dilation and upregulated the expression of ER stress markers GRP78, IRE1α, eIF2α, CHOP, JNK, and p38. Subsequently, we also identified that DR increases the levels of apoptotic fragment of PARP (89 kDa) in breast cancer cells. Blocking the expression of one of the components of the ER stress-mediated apoptosis pathway, CHOP using siRNA significantly decreased DR-induced apoptotic cleavage of PARP. In summary, the present study suggests that the induction of ER stress-mediated apoptosis by DR may account for its cytotoxic effects in human breast cancer cells.
authors.affiliation: Kookmin University, Songbuk-gu, Seoul, Korea.
authors.forename: Thamizhiniyan
authors.initials: T
authors.lastname: Venkatesan
authors.affiliation: Kookmin University, Songbuk-gu, Seoul, Korea.
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Jeong
authors.affiliation: Kookmin University, Songbuk-gu, Seoul, Korea.
authors.forename: Young-Woong
authors.initials: YW
authors.lastname: Choi
authors.affiliation: Kookmin University, Songbuk-gu, Seoul, Korea.
authors.forename: Eun-Jin
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Jazan University, Jazan, Kingdom of Saudi Arabia.|National Research Center, Cairo, Dokki, Egypt.
authors.forename: Samy Korany
authors.initials: SK
authors.lastname: El-Desouky
authors.affiliation: Kookmin University, Songbuk-gu, Seoul, Korea ykkim@kookmin.ac.kr.
authors.forename: Young-Kyoon
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012250:Rheum / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D051742:Transcription Factor CHOP; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D013267:Stilbenes; D051742:Transcription Factor CHOP; D011065:Poly(ADP-ribose) Polymerases
keywords: ER stress; Rheum undulatum L.; apoptosis; breast cancer; chemoresistant; deoxyrhapontigenin