Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells

Sudhakar Chintharlapalli; Sabitha Papineni; Maen Abdelrahim; Ala Abudayyeh; Indira Jutooru; Gayathri Chadalapaka; Fei Wu; Susanne Mertens-Talcott; Kathy Vanderlaag; Dae Cho Sung; Roger Smith; Stephen Safe

doi:10.1002/ijc.24530

Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells

Sudhakar Chintharlapalli, Sabitha Papineni, Maen Abdelrahim, Ala Abudayyeh, Indira Jutooru, Gayathri Chadalapaka, Fei Wu, Susanne Mertens-Talcott, Kathy Vanderlaag, Dae Cho Sung, Roger Smith, Stephen Safe

Research output: Contribution to journal › Article › peer-review

116 Scopus citations

Abstract

Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic derivative of glycyrrhetinic acid, a triterpenoid phytochemical found in licorice extracts. CDODA-Me inhibited growth of RKO and SW480 colon cancer cells and this was accompanied by decreased expression of Sp1, Sp3 and Sp4 protein and mRNA and several Sp-dependent genes including survivin, vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1 or Flt-1). CDODA-Me also induced apoptosis, arrested RKO and SW480 cells at G ₂/M, and inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. CDODA-Me decreased expression of microRNA-27a (miR-27a), and this was accompanied by increased expression of 2 miR-27a-regulated mRNAs, namely ZBTB10 (an Sp repressor) and Myt-1 which catalyzes phosphorylation of cdc2 to inhibit progression of cells through G₂/M. Both CDODA-Me and antisense miR-27a induced comparable responses in RKO and SW480 cells, suggesting that the potent anticarcinogenic activity of CDODA-Me is due to repression of oncogenic miR-27a.

Original language	English (US)
Pages (from-to)	1965-1974
Number of pages	10
Journal	International Journal of Cancer
Volume	125
Issue number	8
DOIs	https://doi.org/10.1002/ijc.24530
State	Published - Oct 15 2009

Keywords

Anticarcinogenicity
CDODA-Me
Cell cycle
Colon cancer
miR-27a

ASJC Scopus subject areas

Oncology
Cancer Research

Divisions

Medical Oncology

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10.1002/ijc.24530

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Chintharlapalli, S., Papineni, S., Abdelrahim, M., Abudayyeh, A., Jutooru, I., Chadalapaka, G., Wu, F., Mertens-Talcott, S., Vanderlaag, K., Sung, D. C., Smith, R., & Safe, S. (2009). Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells. International Journal of Cancer, 125(8), 1965-1974. https://doi.org/10.1002/ijc.24530

Chintharlapalli, S, Papineni, S, Abdelrahim, M, Abudayyeh, A, Jutooru, I, Chadalapaka, G, Wu, F, Mertens-Talcott, S, Vanderlaag, K, Sung, DC, Smith, R & Safe, S 2009, 'Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells', International Journal of Cancer, vol. 125, no. 8, pp. 1965-1974. https://doi.org/10.1002/ijc.24530

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title = "Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells",

abstract = "Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic derivative of glycyrrhetinic acid, a triterpenoid phytochemical found in licorice extracts. CDODA-Me inhibited growth of RKO and SW480 colon cancer cells and this was accompanied by decreased expression of Sp1, Sp3 and Sp4 protein and mRNA and several Sp-dependent genes including survivin, vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1 or Flt-1). CDODA-Me also induced apoptosis, arrested RKO and SW480 cells at G 2/M, and inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. CDODA-Me decreased expression of microRNA-27a (miR-27a), and this was accompanied by increased expression of 2 miR-27a-regulated mRNAs, namely ZBTB10 (an Sp repressor) and Myt-1 which catalyzes phosphorylation of cdc2 to inhibit progression of cells through G2/M. Both CDODA-Me and antisense miR-27a induced comparable responses in RKO and SW480 cells, suggesting that the potent anticarcinogenic activity of CDODA-Me is due to repression of oncogenic miR-27a.",

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AU - Chintharlapalli, Sudhakar

AU - Papineni, Sabitha

AU - Abdelrahim, Maen

AU - Abudayyeh, Ala

AU - Jutooru, Indira

AU - Chadalapaka, Gayathri

AU - Wu, Fei

AU - Mertens-Talcott, Susanne

AU - Vanderlaag, Kathy

AU - Sung, Dae Cho

AU - Smith, Roger

AU - Safe, Stephen

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N2 - Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic derivative of glycyrrhetinic acid, a triterpenoid phytochemical found in licorice extracts. CDODA-Me inhibited growth of RKO and SW480 colon cancer cells and this was accompanied by decreased expression of Sp1, Sp3 and Sp4 protein and mRNA and several Sp-dependent genes including survivin, vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1 or Flt-1). CDODA-Me also induced apoptosis, arrested RKO and SW480 cells at G 2/M, and inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. CDODA-Me decreased expression of microRNA-27a (miR-27a), and this was accompanied by increased expression of 2 miR-27a-regulated mRNAs, namely ZBTB10 (an Sp repressor) and Myt-1 which catalyzes phosphorylation of cdc2 to inhibit progression of cells through G2/M. Both CDODA-Me and antisense miR-27a induced comparable responses in RKO and SW480 cells, suggesting that the potent anticarcinogenic activity of CDODA-Me is due to repression of oncogenic miR-27a.

AB - Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic derivative of glycyrrhetinic acid, a triterpenoid phytochemical found in licorice extracts. CDODA-Me inhibited growth of RKO and SW480 colon cancer cells and this was accompanied by decreased expression of Sp1, Sp3 and Sp4 protein and mRNA and several Sp-dependent genes including survivin, vascular endothelial growth factor (VEGF), and VEGF receptor 1 (VEGFR1 or Flt-1). CDODA-Me also induced apoptosis, arrested RKO and SW480 cells at G 2/M, and inhibited tumor growth in athymic nude mice bearing RKO cells as xenografts. CDODA-Me decreased expression of microRNA-27a (miR-27a), and this was accompanied by increased expression of 2 miR-27a-regulated mRNAs, namely ZBTB10 (an Sp repressor) and Myt-1 which catalyzes phosphorylation of cdc2 to inhibit progression of cells through G2/M. Both CDODA-Me and antisense miR-27a induced comparable responses in RKO and SW480 cells, suggesting that the potent anticarcinogenic activity of CDODA-Me is due to repression of oncogenic miR-27a.

KW - Anticarcinogenicity

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KW - Cell cycle

KW - Colon cancer

KW - miR-27a

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Oncogenic microRNA-27a is a target for anticancer agent methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate in colon cancer cells

Abstract

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