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Anti‐cancer effects of daurinol, a plant arynaphthalane lignan, with low hematological toxicity compared to etoposide
Author(s) -
Kang Kyungsu,
Oh Seung Hyun,
Yun Ji Ho,
Jho Eun Hye,
Kang Ju Hee,
Batsuren Dulamjav,
Tunsag Jigjidsuren,
Park Kwang Hwa,
Nho Chu Won
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.251.8
Subject(s) - etoposide , toxicity , dna damage , pharmacology , cancer cell , in vivo , lignan , cancer research , chemistry , cancer , biology , chemotherapy , medicine , biochemistry , dna , botany , genetics
We investigated the cancer suppression effects of daurinol, a plant lignan from Haplophyllum dauricum , and their molecular mechanism in human colon cancer cells. Myelosuppression is one of the most common and serious side effects of cancer chemotherapy usually caused by chemotherapeutic agents such as etoposide. Etoposide, a topoisomerase II poison, is known to induce G2/M arrest, severe DNA damage, and the formation of giant nuclei in HCT116 cells. We hypothesized that the induction of DNA damage and nuclear enlargement due to abnormal chromosomal conditions could lead to genomic instability resulting in the side effects of etoposide. We found that daurinol inhibits DNA synthesis in HCT116 cells through a catalytic inhibition of human topoisomerase IIα. Daurinol induces S‐phase arrest but did not cause DNA damage or nuclear enlargement in vitro . Finally, we confirmed the in vivo antitumor effects and side effects of daurinol and etoposide in nude mice xenograft models. Daurinol displayed potent antitumor effects without any significant loss of body weight or hematological toxicity, whereas etoposide treatment led to decreased body weight, white blood cell and red blood cell counts. Therefore, daurinol could be a promising potential anticancer agent with low hematological toxicity. Grant Funding Source : This work was supported by an intramural grant from KIST and a grant from the Center Project for Korea‐Mongolia Science and Technology Cooperation, MEST (2U04260), Korea.