Lab Anim Res.  2019 Dec;35(4):194-201. 10.1186/s42826-019-0028-7.

Antitumor effect of TW-37, a BH3 mimetic in human oral cancer

Affiliations
  • 1Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea. efiwdsc@snu.ac.kr
  • 2Laboratory Animal Center, CHA University, CHA Biocomplex, Sampyeong-dong, Seongnam 13488, Republic of Korea. jnbhwan@cha.ac.kr
  • 3Chaon, 301-3, 240, Pangyoyeok-ro, Bundang-gu, Seongnam 13493, Republic of Korea.

Abstract

TW-37 is a small molecule B cell lymphoma-2 (Bcl-2) homology 3 mimetic with potential anticancer activities. However, the in vivo anti-cancer effect of TW-37 in human oral cancer has not been properly studied yet. Here, we attempted to confirm antitumor activity of TW37 in human oral cancer. TW-37 significantly inhibited cell proliferation and increased the number of dead cells in MC-3 and HSC-3 human oral cancer cell lines. TW-37 enhanced apoptosis of both cell lines evidenced by annexin V/propidium iodide double staining, sub-G1 population analysis and the detection of cleaved poly (ADP-ribose) polymerase and caspase-3. In addition, TW-37 markedly downregulated the expression of Bcl-2 protein, while not affecting Bcl-xL or myeloid cell leukemia-1. In vivo, TW-37 inhibited tumor growth in a nude mice xenograft model without any significant liver and kidney toxicities. Collectively, these data reveal that TW-37 may be a promising small molecule to inhibit human oral cancer.

Keyword

TW-37; Apoptosis; Bcl-2; Oral cancer
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