African descents are more sensitive than European descents to the antitumor compounds α-hederin and kalopanaxsaponin I.
α-Hederin, a natural triterpene saponin and its derivative kalopanaxsaponin I (ksI) exhibit cytotoxicity against various cancer cell lines and IN VIVO tumors. We studied the genetic variants contributing to the activity of these two anticancer compounds. Cell lines derived from 30 trios of European descent (Centre d'Etude du Polymorphisme Human, CEPH; CEU) and 30 trios of African descent (Yoruban, YRI) were used. Cytotoxicity was determined as inhibition of cell growth at increasing concentrations of α-hederin or ksI for 24 h. In comparison to the European, the Yoruban populations revealed a higher sensitivity to α-hederin and to ksI that can be attributed to several unique SNPs. These SNPs are located near 111 and 130 genes in the European and the Yoruban populations, respectively, raising the possibility that some of these genes contribute to the differential sensitivity to these compounds.
Feller
Geva
G
Ben Gurion University of the Negev, Bioinformatic Core Facility, National Institute of Biotechnology in the Negev, Beer Sheva, Israel.
Kugel
Aleksandra
A
Moonshine
Dana
D
Chalifa-Caspi
Vered
V
Scholz
Martin
M
Prüfer
Dirk
D
Rabinski
Tatiana
T
Müller
Kai J
KJ
Ofir
Rivka
R
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D044383:Black People / Q000235:genetics*; D045744:Cell Line, Tumor; D006131:Growth Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics*; D031844:Nigella / Q000737:chemistry; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010597:Pharmacogenetics; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D012503:Saponins / Q000494:pharmacology / Q000627:therapeutic use*; D012639:Seeds; D044465:White People / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; D006131:Growth Inhibitors; D010936:Plant Extracts; D012503:Saponins; C010177:beta-hederin; C117027:kalopanax saponin I; D009828:Oleanolic Acid