Shikonin suppresses skin carcinogenesis via inhibiting cell proliferation

Wenjuan Li, Chunjing Zhang, Amy Ren, Teena Li, Rong Jin, Guohong Li, Xin Gu, Runhua Shi, Yunfeng Zhao

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The M2 isoform of pyruvate kinase M2 (PKM2) has been shown to be up-regulated in human skin cancers. To test whether PKM2 may be a target for chemoprevention, shikonin, a natural product from the root of Lithospermum erythrorhizon and a specific inhibitor of PKM2, was used in a chemically-induced mouse skin carcinogenesis study. The results revealed that shikonin treatment suppressed skin tumor formation. Morphological examinations and immunohistochemical staining of the skin epidermal tissues suggested that shikonin inhibited cell proliferation without inducing apoptosis. Although shikonin alone suppressed PKM2 activity, it did not suppress tumor promoter-induced PKM2 activation in the skin epidermal tissues at the end of the skin carcinogenesis study. To reveal the potential chemopreventive mechanism of shikonin, an antibody microarray analysis was performed, and the results showed that the transcription factor ATF2 and its downstream target Cdk4 were up-regulated by chemical carcinogen treatment; whereas these up-regulations were suppressed by shikonin. In a promotable skin cell model, the nuclear levels of ATF2 were increased during tumor promotion, whereas this increase was inhibited by shikonin. Furthermore, knockdown of ATF2 decreased the expression levels of Cdk4 and Fra-1 (a key subunit of the activator protein 1. In summary, these results suggest that shikonin, rather than inhibiting PKM2 in vivo, suppresses the ATF2 pathway in skin carcinogenesis.

Original languageEnglish (US)
Article numbere0126459
JournalPloS one
Volume10
Issue number5
DOIs
StatePublished - May 11 2015

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Cell proliferation
skin (animal)
carcinogenesis
pyruvate kinase
Pyruvate Kinase
cell proliferation
Skin
Carcinogenesis
Cell Proliferation
Carcinogens
Tumors
antibody microarrays
Lithospermum
Activating Transcription Factor 2
Lithospermum erythrorhizon
Tissue
chemoprevention
neoplasms
shikonin
Transcription Factor AP-1

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Li, Wenjuan ; Zhang, Chunjing ; Ren, Amy ; Li, Teena ; Jin, Rong ; Li, Guohong ; Gu, Xin ; Shi, Runhua ; Zhao, Yunfeng. / Shikonin suppresses skin carcinogenesis via inhibiting cell proliferation. In: PloS one. 2015 ; Vol. 10, No. 5.
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Li, W, Zhang, C, Ren, A, Li, T, Jin, R, Li, G, Gu, X, Shi, R & Zhao, Y 2015, 'Shikonin suppresses skin carcinogenesis via inhibiting cell proliferation', PloS one, vol. 10, no. 5, e0126459. https://doi.org/10.1371/journal.pone.0126459

Shikonin suppresses skin carcinogenesis via inhibiting cell proliferation. / Li, Wenjuan; Zhang, Chunjing; Ren, Amy; Li, Teena; Jin, Rong; Li, Guohong; Gu, Xin; Shi, Runhua; Zhao, Yunfeng.

In: PloS one, Vol. 10, No. 5, e0126459, 11.05.2015.

Research output: Contribution to journalArticle

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AU - Li, Wenjuan

AU - Zhang, Chunjing

AU - Ren, Amy

AU - Li, Teena

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AU - Gu, Xin

AU - Shi, Runhua

AU - Zhao, Yunfeng

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