Induction of apoptosis underlies the Radix Rubiae-mediated anti-proliferative action on human epidermal keratinocytes: implications for psoriasis treatment.
Psoriasis is a chronic inflammatory skin disease characterized histologically by hyperproliferation and aberrant differentiation of epidermal keratinocytes. While screening 60 psoriasis-treating Chinese herbs for their anti-proliferative properties using a cultured human HaCaT keratinocyte model, we found Radix Rubiae to be highly effective. Evidence is now provided that induction of apoptosis is the underlying mechanism for the observed anti-proliferative action of Radix Rubiae. Analysis of cell cycle with PI staining showed that Radix Rubiae induced the appearance of a sub-G1 peak and cell arrest at the G1 phase. Radix Rubiae was also capable of inducing morphological changes as evidenced by nuclear condensation. DNA fragmentation was clearly demonstrated by gel electrophoresis and by the TUNEL method. Quantitative analyses by Annexin V-PI staining revealed that Radix Rubiae-induced apoptosis was dose- and time-dependent. Furthermore, Radix Rubiae was able to activate caspase-3 expression when examined by Western blot analysis. The cellular, morphological and molecular data unequivocally demonstrated that induction of cellular apoptosis was mainly responsible for the previously observed anti-proliferation induced Radix Rubiae on HaCaT keratinocytes. Our experimental results suggest that Radix Rubiae is a promising source from which a herb-based topical agent could be developed for psoriasis treatment.
Tse
Wai-Pui
WP
School of Chinese Medicine, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong SAR, P.R. China.
Cheng
Christopher H K
CH
Che
Chun-Tao
CT
Zhao
Ming
M
Lin
Zhi-Xiu
ZX
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D053938:DNA Fragmentation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D011419:Propidium / Q000378:metabolism; D011565:Psoriasis / Q000188:drug therapy*; D011714:Pyrans / Q000494:pharmacology
D017304:Annexin A5; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D011714:Pyrans; D011419:Propidium; C046245:rubimaillin; D053148:Caspase 3