23,24-Dihydrocucurbitacin B induces G2/M cell-cycle arrest and mitochondria-dependent apoptosis in human breast cancer cells (Bcap37).
23,24-Dihydrocucurbitacin B (DHCB), a cucurbitacin-derived compound known to posses anticancer and anti-inflammatory activities. In this study, DHCB, isolated from roots of Trichosanthes kirilowli which is a traditional Chinese herb medicine used as treatments for cancer and other diseases, has been found to inhibit the proliferation of human cancer cell lines Bcap37, HeLa, SW620, SMMC-7721, K562 and MCF-7 in a dose- and time-dependent manner, and induce apoptosis in human breast cancer cell line Bcap37 at low concentration. DHCB-induced Bcap37 apoptosis was characterized with the changes in nuclear morphology, DNA fragmentation, activation of caspase-like activities, poly(ADP-ribose) polymerase cleavage, release of cytochrome c into cytosol. The cell death was partly prevented by a caspase-family inhibitor Z-VAD-FMK. The results suggest that DHCB-induced Bcap37 apoptosis through mitochondrial dependent pathway. Flow cytometric analysis revealed that at the lower dose of 1.8 and 3.6muM, DHCB-induced cancer cell lines death via an apoptotic process rather than necrotic one; whereas, the higher dose of 8.9, 17.9 and 35.7muM induced cell death via the necrotic process. Cell-cycle analysis demonstrated DHCB induction of G(2)/M phase cell-cycle arrest and apoptosis. The overall results suggest that DHCB might have the therapeutic value against human cancer cell lines, especially the breast cancer cell lines.
Yang
Lu
L
Zhejiang University, Research Centre of Siyuan Natural Pharmacy and Biotoxicology, College of Life Sciences, Zijinggang Campus, Hangzhou 310058, PR China.
Wu
Shihua
S
Zhang
Qiuhui
Q
Liu
Feiyan
F
Wu
Ping
P
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D005260:Female; D016195:G2 Phase / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D020014:K562 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D018517:Plant Roots; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D000091402:Prohibitins; D029778:Trichosanthes / Q000737:chemistry; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use
D000590:Amino Acid Chloromethyl Ketones; D000972:Antineoplastic Agents, Phytogenic; D015853:Cysteine Proteinase Inhibitors; C000717331:PHB2 protein, human; D000091402:Prohibitins; D014315:Triterpenes; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; C478086:23,24-dihydrocucurbitacin B