Anti-tumor activities and mechanism study of α-pinene derivative in vivo and in vitro
In previous study, we designed novel α-pinene derivatives based on theories of bioalkylating agents using α-pinene as lead compound and patented these compounds, in which compound α-pinene derivative GY-1 (6,6-dimethylbicyclo[3.1.1]hept-2-en-2-yl)methyl-4-methylbenzenesulfonat) showed strongest inhibition on hepatoma carcinoma cell BEL-7402. In this study, we investigated effect of GY-1 on hepatocellular carcinoma in vitro and in vivo, and explored its mechanism of anti-hepatoma. The results showed that GY-1 showed good anti-liver cancer activity with the IC50 of 84.7 μmol/L in vitro, inhibited tumor growth in vivo with dose-dependent, and GY-1 could arrest the growth of hepatoma cells in the S phase and induced apoptosis in hepatoma cells, down-regulated the expression of C-myc, CDK2 and CyclinE, and up-regulate p53.
Keywordsα-Pinene derivative Anti-hepatoma activity Anti-hepatoma mechanism Apoptosis Cell cycle
The work was supported by Special Innovation Project of Guangdong Education Department (Natural Science) (2017KTSCX107), Guangdong Natural Science Foundation (2015A03031356, 2015A030310176), Science and Technology Planning Project of Guangdong Province (2016A020215159,2017ZC0199), Medical Scientific Research Foundation of Guangdong province (B2019004), Key laboratory of new drug discovery and evaluation of ordinary universities of Guangdong province(2017KSYS002), Guangzhou key laboratory of construction and application of new drug screening model systems(201805010006), Guangdong province precise medicine and big data engineering technology research center for traditional Chinese medicine, the open project foundation of the Fujian Provincial Key Laboratory of Theoretical and Computational Chemistry (201502), Guangdong province engineering technology center for molecular probes and biomedical imaging.
WC and LY contributed to the conception and design of the experiments, analysis of the data and revised the paper. WG selected and analyzed the data. QX, XZ, YC, performed the biological studies.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
Ethics approval and consent to participate
The current study was not required to complete an ethical assessment.
- 4.Li P, Liu YP (2001) The research progress of pine needles. J Chengdu Univ Tradit Chin Med. 24:49–50Google Scholar
- 5.Li SZ (1982) Compendium of Materia Medica (Rudin) [M]. Beijing: People's. Medical Publishing House, pp 882–917Google Scholar
- 8.Yang MD, Xu QX, Ye LB, Li M, Feng Y, Chen WQ (2018) Synthesis, biological activity, computer aided drug design of alpha-pinene derivatives. China J Chin Mater Med 5:1001–1007Google Scholar
- 10.Zhu H, Mao ZH, Ding J (2007) ATM, ATR and DNA damage-induced cell cycle arrest. Chin Bull Life Sci 2:139–148Google Scholar
- 11.Huang YX, Chen XT, Guo KY (2015) Molecular mechanism of multi-target tyrosine kinase inhibitors-combined with NK cells againest human hepatocellular carcinoma. Chin J Cancer Biother 6:675–683Google Scholar
- 12.Jin ZY, Zheng CL, Zheng H (2002) Expression of PTTG protein and c-myc protein in primary human hepatocellular carcinoma. China J Mod Med 17:11–13Google Scholar
- 17.Fu M, Wang C, Li Z et al (2005) Cyclin D1: normal and Abnormal Functions. Endocrinology 12:5439–5447Google Scholar