5-Nitro-5'-hydroxy-indirubin-3'-oxime (AGM130), an indirubin-3'-oxime derivative, inhibits tumor growth by inducing apoptosis against non-small cell lung cancer in vitro and in vivo.
This study examined the anti-tumor effects of AGM130, a novel indirubin-3'-oxime derivative in A549 human non-small cell lung cancer cells. AGM130 significantly inhibited the proliferation and arrested the cell cycle of G2/M phase. Induction of apoptosis was detected in AGM130-treated A549 cells. The protein levels of Cytochrome c release, Bax, cleaved caspases and PARP were increased in AGM130 treated cells, whereas Bcl-2 levels were decreased. AGM130 inhibited Insulin-like growth factor 1 receptor (IGF1R), AKT/mTOR signaling and inactivated mitogen-activated protein kinases (MAPK). AGM130 also induced slight autophagy as pro-survival function and autophagy inhibition by chloroquine (CQ) induced necrosis. In vivo tumor xenograft model, AGM130 dose-dependently suppressed transplanted A549 cell tumor growth and induced the expression of proliferative cell nuclear antigen (PCNA). AGM130 also increased TUNEL positive apoptotic cell populations and the induction of glandular differentiation with mucin pool compared with vehicle-treated control in tumor tissue. These results suggest that AGM130 is an effective novel indirubin-3'-oxime derivative of anti-cancer drug and may be an attractive candidate for non-small cell lung cancer therapy.
Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Republic of Korea.
Mee-Young
MY
Ahn
Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Tae-Hyung
TH
Kim
Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Republic of Korea.
Seong-Min
SM
Kwon
Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Republic of Korea.
Hyo-Eun
HE
Yoon
Division of Toxicology, School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Hyung-Sik
HS
Kim
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea; Division of Drug Discovery, Anygen Co., Ltd., Gwangju 500-712, Republic of Korea.
Jae-Il
JI
Kim
School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea; Division of Drug Discovery, Anygen Co., Ltd., Gwangju 500-712, Republic of Korea.
Yong-Chul
YC
Kim
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
Keon-Wook
KW
Kang
Department of Pathology, College of Dentistry, Chosun University, Gwangju 501-759, Republic of Korea.
Sang-Gun
SG
Ahn
Department of Oral & Maxillofacial Pathology, College of Dentistry, Wonkwang Bone Regeneration Research Institute, Daejeon Dental Hospital, Wonkwang University, Daejeon 302-120, Republic of Korea. Electronic address: opathyoon@wku.ac.kr.
Jung-Hoon
JH
Yoon
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use*; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors
C000609730:5-nitro-5'-hydroxyindirubin-3'-oxime; D000970:Antineoplastic Agents; C000597236:IGF1R protein, human; D007211:Indoles; D010091:Oximes; D017451:Receptors, Somatomedin; C474021:indirubin-3'-monoxime; D017526:Receptor, IGF Type 1; D051058:Oncogene Protein v-akt
AGM130; Apoptosis; Autophagy; Indirubin derivative; Non-small cell lung cancer