Abstract

The problem of therapeutic resistance and chemotherapeutic efficacy is tricky and critical in the management of colorectal cancer (CRC). Curcumin is a promising anti-cancer agent. Heat shock protein 27 (HSP27) is correlated with CRC progression and is said to affect CRC response to different therapies. However, the role of HSP27 on the therapeutic efficacy of curcumin remains unknown. HSP27 was silenced using small hairpin RNA (shRNA) technique. The cytotoxic and apoptotic effects of curcumin were assessed by sulforhodamine B (SRB) colorimetric assay, flow cytometric cell cycle analysis, and annexin V/propidium iodide (PI) double-labeling assays. Total reactive oxygen species (ROS)/superoxide and autophagy detection were performed, and the levels of apoptosis-related proteins were examined by Western blotting. It was found that the silencing of HSP27 (HSP27-KD) resulted in increased treatment resistance to curcumin in CRC cells. In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in anti-apoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. This was also followed by low reactive oxygen/nitrogen species (ROS/RNS), superoxide and autophagy induction levels in the HSP27-KD cells as compared to the control cells. Therefore, as silencing of HSP27 increases curcumin resistance by reducing apoptosis and reactive oxidative stress production, HSP27 is a potential selective target for curcumin treatment in CRC.

Original languageEnglish
Pages (from-to)43-51
Number of pages9
JournalLife Sciences
Volume209
DOIs
Publication statusPublished - Sep 15 2018

Fingerprint

HSP27 Heat-Shock Proteins
Curcumin
Autophagy
Colonic Neoplasms
Reactive Oxygen Species
Chemical activation
Cells
Colorectal Neoplasms
Neoplasms
Apoptosis Regulatory Proteins
Apoptosis
lissamine rhodamine B
Superoxides
Assays
Cell Cycle
Reactive Nitrogen Species
Oxidative stress
Propidium
G2 Phase
Annexin A5

Keywords

  • Apoptosis
  • Autophagy
  • Colorectal cancer
  • Curcumin
  • HSP27
  • Reactive oxygen species
  • Resistance

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation. / Liang, Hung Hua; Huang, Chien Yu; Chou, Ching Wen; Makondi, Precious Takondwa; Huang, Ming Te; Wei, Po Li; Chang, Yu Jia.

In: Life Sciences, Vol. 209, 15.09.2018, p. 43-51.

Research output: Contribution to journalArticle

@article{5eb3ae002382425ba820c1251cb10308,
title = "Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation",
abstract = "The problem of therapeutic resistance and chemotherapeutic efficacy is tricky and critical in the management of colorectal cancer (CRC). Curcumin is a promising anti-cancer agent. Heat shock protein 27 (HSP27) is correlated with CRC progression and is said to affect CRC response to different therapies. However, the role of HSP27 on the therapeutic efficacy of curcumin remains unknown. HSP27 was silenced using small hairpin RNA (shRNA) technique. The cytotoxic and apoptotic effects of curcumin were assessed by sulforhodamine B (SRB) colorimetric assay, flow cytometric cell cycle analysis, and annexin V/propidium iodide (PI) double-labeling assays. Total reactive oxygen species (ROS)/superoxide and autophagy detection were performed, and the levels of apoptosis-related proteins were examined by Western blotting. It was found that the silencing of HSP27 (HSP27-KD) resulted in increased treatment resistance to curcumin in CRC cells. In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in anti-apoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. This was also followed by low reactive oxygen/nitrogen species (ROS/RNS), superoxide and autophagy induction levels in the HSP27-KD cells as compared to the control cells. Therefore, as silencing of HSP27 increases curcumin resistance by reducing apoptosis and reactive oxidative stress production, HSP27 is a potential selective target for curcumin treatment in CRC.",
keywords = "Apoptosis, Autophagy, Colorectal cancer, Curcumin, HSP27, Reactive oxygen species, Resistance",
author = "Liang, {Hung Hua} and Huang, {Chien Yu} and Chou, {Ching Wen} and Makondi, {Precious Takondwa} and Huang, {Ming Te} and Wei, {Po Li} and Chang, {Yu Jia}",
year = "2018",
month = "9",
day = "15",
doi = "10.1016/j.lfs.2018.07.047",
language = "English",
volume = "209",
pages = "43--51",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Heat shock protein 27 influences the anti-cancer effect of curcumin in colon cancer cells through ROS production and autophagy activation

AU - Liang, Hung Hua

AU - Huang, Chien Yu

AU - Chou, Ching Wen

AU - Makondi, Precious Takondwa

AU - Huang, Ming Te

AU - Wei, Po Li

AU - Chang, Yu Jia

PY - 2018/9/15

Y1 - 2018/9/15

N2 - The problem of therapeutic resistance and chemotherapeutic efficacy is tricky and critical in the management of colorectal cancer (CRC). Curcumin is a promising anti-cancer agent. Heat shock protein 27 (HSP27) is correlated with CRC progression and is said to affect CRC response to different therapies. However, the role of HSP27 on the therapeutic efficacy of curcumin remains unknown. HSP27 was silenced using small hairpin RNA (shRNA) technique. The cytotoxic and apoptotic effects of curcumin were assessed by sulforhodamine B (SRB) colorimetric assay, flow cytometric cell cycle analysis, and annexin V/propidium iodide (PI) double-labeling assays. Total reactive oxygen species (ROS)/superoxide and autophagy detection were performed, and the levels of apoptosis-related proteins were examined by Western blotting. It was found that the silencing of HSP27 (HSP27-KD) resulted in increased treatment resistance to curcumin in CRC cells. In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in anti-apoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. This was also followed by low reactive oxygen/nitrogen species (ROS/RNS), superoxide and autophagy induction levels in the HSP27-KD cells as compared to the control cells. Therefore, as silencing of HSP27 increases curcumin resistance by reducing apoptosis and reactive oxidative stress production, HSP27 is a potential selective target for curcumin treatment in CRC.

AB - The problem of therapeutic resistance and chemotherapeutic efficacy is tricky and critical in the management of colorectal cancer (CRC). Curcumin is a promising anti-cancer agent. Heat shock protein 27 (HSP27) is correlated with CRC progression and is said to affect CRC response to different therapies. However, the role of HSP27 on the therapeutic efficacy of curcumin remains unknown. HSP27 was silenced using small hairpin RNA (shRNA) technique. The cytotoxic and apoptotic effects of curcumin were assessed by sulforhodamine B (SRB) colorimetric assay, flow cytometric cell cycle analysis, and annexin V/propidium iodide (PI) double-labeling assays. Total reactive oxygen species (ROS)/superoxide and autophagy detection were performed, and the levels of apoptosis-related proteins were examined by Western blotting. It was found that the silencing of HSP27 (HSP27-KD) resulted in increased treatment resistance to curcumin in CRC cells. In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in anti-apoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. This was also followed by low reactive oxygen/nitrogen species (ROS/RNS), superoxide and autophagy induction levels in the HSP27-KD cells as compared to the control cells. Therefore, as silencing of HSP27 increases curcumin resistance by reducing apoptosis and reactive oxidative stress production, HSP27 is a potential selective target for curcumin treatment in CRC.

KW - Apoptosis

KW - Autophagy

KW - Colorectal cancer

KW - Curcumin

KW - HSP27

KW - Reactive oxygen species

KW - Resistance

UR - http://www.scopus.com/inward/record.url?scp=85050886475&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050886475&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2018.07.047

DO - 10.1016/j.lfs.2018.07.047

M3 - Article

AN - SCOPUS:85050886475

VL - 209

SP - 43

EP - 51

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -