2. Academic Validation
  3. The inhibitory effect of kokusaginine on the growth of human breast cancer cells and MDR-resistant cells is mediated by the inhibition of tubulin assembly

The inhibitory effect of kokusaginine on the growth of human breast cancer cells and MDR-resistant cells is mediated by the inhibition of tubulin assembly

  • Bioorg Med Chem Lett. 2018 Aug 1;28(14):2490-2492. doi: 10.1016/j.bmcl.2018.05.059.
Hao Chen 1,  Shuguo Li 2,  Shuibin Wang 3,  Weiping Li 3,  Ning Bao 3,  Wenbin Ai 4
Affiliations

Affiliations

  • 1 The First People's Hospital of Jiangxia District, Wuhan 430200, Hubei, China. Electronic address: [email protected].
  • 2 Institute of Gerontology, China Three Gorges University, Yichang 443002, Hubei, China; People's Hospital of Yichang Center, Yichang 443003, Hubei, China.
  • 3 Yichang Yiling Hospital, 32# Donghu Avenue, Yichang 443100, Hubei, China.
  • 4 Yichang Yiling Hospital, 32# Donghu Avenue, Yichang 443100, Hubei, China. Electronic address: [email protected].
PMID: 29903663 DOI: 10.1016/j.bmcl.2018.05.059
Abstract

The emergence of multidrug resistance (MDR) is a significant challenge in breast carcinoma chemotherapy. Kokusaginine isolated from Dictamnus dasycarpus Turcz. has been reported to show cytotoxicity in several human Cancer cell lines including breast Cancer cells MCF-7. In this study, kokusaginine showed the potent inhibitory effect on MCF-7 multidrug resistant subline MCF-7/ADR and MDA-MB-231 multidrug resistant subline MDA-MB-231/ADR. Kokusaginine markedly induced Apoptosis in a concentration-dependent manner in MCF-7/ADR cells. Furthermore, kokusaginine reduced P-gp mRNA and protein levels, and suppressed P-gp function especially in MCF-7/ADR cells. In addition, kokusaginine showed to inhibit tubulin assembly and the binding of colchicine to tubulin by binding directly to tubulin and affects tubulin formation in vitro. Taken together, these results support the potential therapeutic value of kokusaginine as an anti-MDR agent in chemotherapy for breast carcinoma.

Keywords

Breast cancer; Kokusaginine; Multidrug resistance; P-gp; Tubulin.

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