Growth inhibition and induction of G1 phase cell cycle arrest in human lung cancer cells by a phenylbutenoid dimer isolated from Zingiber cassumunar.
In our previous study, a novel phenylbutenoid dimer (+/-)-trans-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene (PSC), isolated from Zingiber cassumunar ROXB. (Zingiberaceae), inhibited proliferation of various human cancer cells with the IC(50) values ranging 10 to 30 microM. Prompted by these anti-proliferative effects, we performed additional studies in A549 human lung cancer cells in order to investigate the mechanism of action. PSC arrested cell cycle progression at the G0/G1 phase in a concentration- and time-dependent manner. PSC dose-dependently induced cyclin-dependent kinase (CDK) inhibitor p21 expression, whereas the expression of cyclin D1, cyclin A, CDK4, CDK2, and proliferating cell nuclear antigen (PCNA) were decreased by treatment with PSC. These results suggest that one of the anti-proliferative mechanisms of PSC is to suppress cell cycle progression by increasing p21 expression and down-regulating cyclins and CDKs. This study characterizes additional biological activity of this novel phenylbutenoid dimer and expands its therapeutic potential for cancer as a chemotherapeutic agent derived from natural products.
College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-ku, Seoul 120-750, Korea.
Jong-Won
JW
Lee
Hye-Young
HY
Min
Ah-Reum
AR
Han
Hwa-Jin
HJ
Chung
Eun-Jung
EJ
Park
Hyen Joo
HJ
Park
Ji-Young
JY
Hong
Eun-Kyoung
EK
Seo
Sang Kook
SK
Lee
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053138:Cyclohexenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D016193:G1 Phase / Q000187:drug effects*; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013343:Styrenes
D000972:Antineoplastic Agents, Phytogenic; D018797:Cell Cycle Proteins; D053138:Cyclohexenes; C522789:trans-3-(3,4-dimethoxyphenyl)-4-((E)-3,4-dimethoxystyryl)cyclohex-1-ene; D013343:Styrenes