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Vitiligo is a depigmentation disorder of the skin. It is primarily caused by the destruction of melanocytes or obstruction of the melanin synthesis pathway. Melanin is a type of skin pigment that determines skin color. The seeds of Vernonia anthelmintica (L.) Willd (Kaliziri) are used for treating skin diseases including vitiligo in traditional Uyghur medicine. 1,5‑Dicaffeoylquinic acid (1,5‑diCQA) is a natural polyphenolic compound widely distributed in plants and extracted from Kaliziri seeds. Therefore, in the present study, the effect of 1,5‑diCQA on melanin synthesis in B16 cell was evaluated, and its molecular mechanism was explored. The results indicated that 1,5‑diCQA treatment of B16 cells stimulated an increase of intracellular melanin level and tyrosinase (TYR) activity without cytotoxicity. Reverse transcription quantitative polymerase chain reaction results also indicated that 1,5‑diCQA may markedly improve the protein expression and RNA transcription of microphthalmia‑associated transcription factor (MITF), melanogenic enzyme Tyr, tyrosinase‑related protein 1 (TRP 1) and tyrosinase‑related protein 2 (TRP 2). Additional results identified that 1,5‑diCQA may promote the phosphorylation of p38 mitogen‑activated protein kinase (p38 MAPK) and extracellular signal‑regulated kinase (ERK) MAPK. Notably, the increased levels of intracellular melanin synthesis and tyrosinase expression induced by 1,5‑diCQA treatment were significantly attenuated by the protein kinase A (PKA) inhibitor H‑89. Intracellular cyclic adenosine monophosphate (cAMP) concentration and phosphorylation of cAMP‑response element binding protein was increased following 1,5‑diCQA treatment. These results indicated that 1,5‑diCQA stimulated melanogenesis via the MAPK and cAMP/PKA signaling pathways in B16 cells, which has potential therapeutic implications for vitiligo.

Homoharringtonine (HHT) and imatinib have a synergistic effect in the clinical treatment of chronic myeloid leukemia (CML). The purpose of the present study was to explore the underlying mechanisms by which HHT enhanced imatinib sensitivity. K562 CML cells were treated with HHT and imatinib separately or in combination. Cell viability was detected by Cell Counting Kit‑8 assay; apoptotic rates and protein expression levels of phosphorylated‑tyrosine (p‑Tyr) and p‑CRK like proto‑oncogene, adaptor protein (p‑Crkl) were analyzed by flow cytometry; zinc‑finger protein, X‑linked (ZFX) overexpression plasmid was transfected to cells using electroporation; western blotting was used to detect the protein expression levels of PI3K, AKT, p‑AKT and ZFX; and reverse transcription‑quantitative PCR was used to measure ZFX mRNA expression levels. The results demonstrated that HHT and imatinib co‑treatment had significant effects of proliferation inhibition and apoptosis induction on K562 CML cells compared with imatinib alone. Co‑treatment also significantly downregulated the expression levels of p‑Tyr, p‑Crkl, PI3K and p‑Akt compared with imatinib or HHT treatment. In addition, HHT downregulated ZFX mRNA and protein expression. ZFX overexpression reversed cell sensitivity to imatinib and HHT and also reduced the HHT‑induced imatinib sensitization by increasing p‑Akt expression. In conclusion, HHT may enhance the effect of imatinib on CML cells by downregulating ZFX.

To explore the in vivo anticancer effects of luteolin with BGC-823 gastric carcinoma xenografts in nude mice and elucidate its mechanism.After modeling of gastric carcinoma xenografts in nude mice, 40 BALB/c (nu/nu) nude mice were randomly divided into 5 groups (n = 8 each). And an intraperitoneal injection of luteolin was administered at 10 mg/kg (low-dose), 20 mg/kg (middle-dose) and 40 mg/kg (high-dose) groups. And 5-fluorouracil (30 mg/kg) and control groups were also established. The growth curves of xenografts in nude mice were drawn and weight inhibition rates measured. The morphological features were detected by hematoxylin and eosin staining. And the protein expression levels of vascular endothelial growth factor A (VEGF-A) and matrix metalloproteinase 9 (MMP-9) were measured by immunohistochemistry.In vivo tumor formation test showed that tumor volume in nude mice treated with luteolin was smaller than that of control group. Tumor weights of high-dose luteolin group were lighter than those of the control ((0.29 ± 0.01) vs (0.38 ± 0.03) g). And the difference was statistically significant (P0.01). The rate of tumor inhibition in high-dose luteolin group was up to 24.87%. Lymphocytic invasion of tumor tissue was observed under light microscope in the treatment groups. Results of immunohistochemistry showed the positive cell integral of VEGF in middle and high-dose luteolin groups were 1.25 ± 0.17 and 1.00 ± 0.07 respectively. Both were significantly lower than that of control group (1.50 ± 0.15, both P0.05). The positive cell integral of MMP-9 in high-dose luteolin group was markedly lower than that of control group (3.75 ± 1.43 vs 9.00 ± 1.08, P0.01).Luteolin can effectively inhibit the in vivo growth of gastric tumor. The mechanism may be correlated with the stimulation of immune response and the down-regulated expressions of VEGF-A and MMP-9.