Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition

Cheng Chin Chung; Tung Yung Huang; Hung Ru Chu; Roberto De Luca; Elena Candelotti; Chi Hung Huang; Yu Chen S.H. Yang; Sandra Incerpi; Jens Z. Pedersen; Chi Yu Lin; Haw Ming Huang; Sheng Yang Lee; Zi Lin Li; Chun A. ChangOu; Wen Shan Li; Paul J. Davis; Hung Yun Lin; Jacqueline Whang-Peng; Kuan Wang

doi:10.1016/j.fct.2022.112850

Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition

Cheng Chin Chung, Tung Yung Huang, Hung Ru Chu, Roberto De Luca, Elena Candelotti, Chi Hung Huang, Yu Chen S.H. Yang, Sandra Incerpi, Jens Z. Pedersen, Chi Yu Lin, Haw Ming Huang, Sheng Yang Lee, Zi Lin Li, Chun A. ChangOu, Wen Shan Li, Paul J. Davis, Hung Yun Lin, Jacqueline Whang-Peng, Kuan Wang

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

9 Citations (Scopus)

Abstract

The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.

Original language	English
Article number	112850
Journal	Food and Chemical Toxicology
Volume	161
DOIs	https://doi.org/10.1016/j.fct.2022.112850
Publication status	Published - Mar 2022

Keywords

Cell growth
ERK1/2
Heteronemin
NDAT
Non-small cell lung cancer
STAT3
Tetrac

ASJC Scopus subject areas

Food Science
Toxicology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.fct.2022.112850

Cite this

Chung, C. C., Huang, T. Y., Chu, H. R., De Luca, R., Candelotti, E., Huang, C. H., Yang, Y. C. S. H., Incerpi, S., Pedersen, J. Z., Lin, C. Y., Huang, H. M., Lee, S. Y., Li, Z. L., ChangOu, C. A., Li, W. S., Davis, P. J., Lin, H. Y., Whang-Peng, J., & Wang, K. (2022). Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition. Food and Chemical Toxicology, 161, Article 112850. https://doi.org/10.1016/j.fct.2022.112850

Chung, CC, Huang, TY, Chu, HR, De Luca, R, Candelotti, E, Huang, CH, Yang, YCSH, Incerpi, S, Pedersen, JZ, Lin, CY, Huang, HM , Lee, SY, Li, ZL, ChangOu, CA, Li, WS, Davis, PJ, Lin, HY , Whang-Peng, J & Wang, K 2022, 'Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition', Food and Chemical Toxicology, vol. 161, 112850. https://doi.org/10.1016/j.fct.2022.112850

@article{d98bfa95c21940df8cb018e06013cc26,

title = "Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition",

abstract = "The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.",

keywords = "Cell growth, ERK1/2, Heteronemin, NDAT, Non-small cell lung cancer, STAT3, Tetrac",

author = "Chung, {Cheng Chin} and Huang, {Tung Yung} and Chu, {Hung Ru} and {De Luca}, Roberto and Elena Candelotti and Huang, {Chi Hung} and Yang, {Yu Chen S.H.} and Sandra Incerpi and Pedersen, {Jens Z.} and Lin, {Chi Yu} and Huang, {Haw Ming} and Lee, {Sheng Yang} and Li, {Zi Lin} and ChangOu, {Chun A.} and Li, {Wen Shan} and Davis, {Paul J.} and Lin, {Hung Yun} and Jacqueline Whang-Peng and Kuan Wang",

note = "Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = mar,

doi = "10.1016/j.fct.2022.112850",

language = "English",

volume = "161",

journal = "Food and Chemical Toxicology",

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T1 - Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition

AU - Chung, Cheng Chin

AU - Huang, Tung Yung

AU - Chu, Hung Ru

AU - De Luca, Roberto

AU - Candelotti, Elena

AU - Huang, Chi Hung

AU - Yang, Yu Chen S.H.

AU - Incerpi, Sandra

AU - Pedersen, Jens Z.

AU - Lin, Chi Yu

AU - Huang, Haw Ming

AU - Lee, Sheng Yang

AU - Li, Zi Lin

AU - ChangOu, Chun A.

AU - Li, Wen Shan

AU - Davis, Paul J.

AU - Lin, Hung Yun

AU - Whang-Peng, Jacqueline

AU - Wang, Kuan

PY - 2022/3

Y1 - 2022/3

N2 - The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.

AB - The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.

KW - Cell growth

KW - ERK1/2

KW - Heteronemin

KW - NDAT

KW - Non-small cell lung cancer

KW - STAT3

KW - Tetrac

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M3 - Article

C2 - 35151786

AN - SCOPUS:85124652099

SN - 0278-6915

VL - 161

JO - Food and Chemical Toxicology

JF - Food and Chemical Toxicology

M1 - 112850

ER -

Heteronemin and tetrac derivatives suppress non-small cell lung cancer growth via ERK1/2 inhibition

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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