2,2'-Methylenebis (6-tert-butyl 4-methylphenol) enhances the antitumor efficacy of belotecan, a derivative of camptothecin, by inducing autophagy

Minsu Jang, Hyunju Kim, Rackhyun Park, Daum Jo, Eun Ju Lee, Won Keun Oh, Junsoo Park

Research output: Contribution to journalArticle

Abstract

Autophagy regulation is important for tumor cell survival. Activation and inhibition of autophagy can sensitize tumor cells to anticancer drugs. However, few autophagyregulating small molecules are available to increase the efficacy of anticancer drugs. Here, we report that 2,2'-methylenebis (6-tert-butyl 4-methylphenol), hereafter referred to as methylenebis, is a novel autophagy-regulating small molecule that sensitizes tumor cells to belotecan, which is a derivative of camptothecin, a topoisomerase I inhibitor. Methylenebis activates autophagic flux by increasing the level of LC3-II and forming autolysosome puncta. Moreover, methylenebis enhances the antitumor efficacy of belotecan by activating both autophagy and apoptosis. Interestingly, methylenebis increased the level of LC3-II and belotecan independently decreased the level of p62, suggesting that methylenebis and belotecan target different steps of autophagy. Finally, we searched for compounds that are structurally similar to methylenebis. Our results imply that the specific structure of methylenebis contributes to its ability to activate autophagy.

Original languageEnglish
Pages (from-to)115068-115078
Number of pages11
JournalOncotarget
Volume8
Issue number70
DOIs
Publication statusPublished - 2017 Jan 1

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Camptothecin
Autophagy
Topoisomerase I Inhibitors
Neoplasms
Pharmaceutical Preparations
belotecan
4-cresol
Cell Survival
Apoptosis

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Jang, Minsu ; Kim, Hyunju ; Park, Rackhyun ; Jo, Daum ; Lee, Eun Ju ; Oh, Won Keun ; Park, Junsoo. / 2,2'-Methylenebis (6-tert-butyl 4-methylphenol) enhances the antitumor efficacy of belotecan, a derivative of camptothecin, by inducing autophagy. In: Oncotarget. 2017 ; Vol. 8, No. 70. pp. 115068-115078.
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2,2'-Methylenebis (6-tert-butyl 4-methylphenol) enhances the antitumor efficacy of belotecan, a derivative of camptothecin, by inducing autophagy. / Jang, Minsu; Kim, Hyunju; Park, Rackhyun; Jo, Daum; Lee, Eun Ju; Oh, Won Keun; Park, Junsoo.

In: Oncotarget, Vol. 8, No. 70, 01.01.2017, p. 115068-115078.

Research output: Contribution to journalArticle

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AU - Kim, Hyunju

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AU - Jo, Daum

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AU - Oh, Won Keun

AU - Park, Junsoo

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