Kaempferol Promotes Apoptosis While Inhibiting Cell Proliferation via Androgen-Dependent Pathway and Suppressing Vasculogenic Mimicry and Invasion in Prostate Cancer
Kaempferol Promotes Apoptosis While Inhibiting Cell Proliferation via Androgen-Dependent Pathway and Suppressing Vasculogenic Mimicry and Invasion in Prostate Cancer
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DOI：
10.1155/2019/1907698
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发表时间：
2019-12-01
影响因子：
3.2
通讯作者：
Wang, Zhong
中科院分区：
文献类型：
--
作者：
Da, Jun;Xu, Mingxi;Wang, Zhong
山奈酚是一种广为人知的天然黄酮醇，据报道可用于多种癌症的潜在治疗。在本研究中，我们发现5 mU M山奈酚对雄激素敏感的LNCaP细胞生长抑制33%，10 mU山奈酚抑制约60%，15 mU山奈酚几乎100%。山奈酚对PC-3细胞和非恶性RWPE-1细胞的作用也相对有限。在DHT存在下，山奈酚对LNCaP细胞、PC-3细胞和RWPE-1细胞的IC50分别为28.8+/-1.5mU、58.3+/-3.5mU和69.1+/-1.2mU。在双氢睾酮(DHT)存在下，山奈酚以剂量依赖的方式促进LNCaP细胞的凋亡。荧光素酶测定结果表明，山奈酚能显著抑制DHT诱导的雄激素受体的激活。在qPCR数据中，雄激素受体的下游靶点，如PSA、TMPRSS2和TMEPA1，在山奈酚的存在下被发现减少。随后证实PSA的蛋白水平降低。山奈酚抑制AR蛋白表达和核积聚。在一项体外研究中，山奈酚抑制PC-3细胞的血管生成拟态。总而言之，山奈酚是治疗前列腺癌的一种很有前途的候选药物，因为前列腺癌涉及雄激素信号通路和血管生成拟态。
Kaempferol is a well-known natural flavonol reported to be a potential treatment for multiple cancers. In this study, we demonstrated that cell growth of androgen-sensitive LNCaP cells could be inhibited 33% by 5 mu M kaempferol, around 60% by 10 mu M kaempferol, and almost 100% by 15 mu M kaempferol. Also, kaempferol showed relatively limited effect on PC-3 cells and nonmalignant RWPE-1 cells. In the presence of DHT, the IC50 for kaempferol was 28.8 +/- 1.5 mu M in LNCaP cells, 58.3 +/- 3.5 mu M in PC-3 cells, and 69.1 +/- 1.2 mu M in RWPE-1 cells, respectively. Kaempferol promotes apoptosis of LNCaP cells in a dose-dependent manner in the presence of dihydrotestosterone (DHT). Then, luciferase assay data showed that kaempferol could inhibit the activation of androgen receptors induced by DHT significantly. The downstream targets of androgen receptors, such as PSA, TMPRSS2, and TMEPA1, were found decreased in the presence of kaempferol in qPCR data. It was then confirmed that the protein level of PSA was decreased. Kaempferol inhibits AR protein expression and nuclear accumulation. Kaempferol suppressed vasculogenic mimicry of PC-3 cells in an in vitro study. In conclusion, kaempferol is a promising therapeutic candidate for treatment of prostate cancer, where the androgen signaling pathway as well as vasculogenic mimicry are involved.