Vitexin confers HSF-1 mediated autophagic cell death by activating JNK and ApoL1 in colorectal carcinoma cells

Monika Bhardwaj, Souren Paul, Rekha Jakhar, Imran Khan, Ji In Kang, Ho Min Kim, Jong Won Yun, Seon Jin Lee, Hee Jun Cho, Hee Gu Lee, Sun Chul Kang

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome against the alterations in protein homeostasis generated by their hostile tumor microenvironment. Contrasting with the classical induction of heat shock proteins, the pro-oncogenic activities of HSF-1 remains to be explored. Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a potential therapeutic target and novel biomarker by natural compounds. Vitexin, a natural flavonoid has been documented as a potent anti-tumor agent on various cell lines. However, in the present study, when human colorectal carcinoma HCT-116 cells were exposed to vitexin, the induction of HSF-1 downstream target proteins, such as heat shock proteins were suppressed. We identified HSF-1 as a potential molecular target of vitexin that interact with DNA-binding domain of HSF-1, which inhibited HSF-1 oligomerization and activation (in silico). Consequently, HSF-1 hyperphosphorylation mediated by JNK operation causes transcriptional inactivation of HSF-1, and supported ROS-mediated autophagy induction. Interestingly, in HSF-1 immunoprecipitated and silenced HCT-116 cells, co-expression of apolipoprotein 1 (ApoL1) and JNK was observed which promoted the caspase independent autophagic cell death accompanied by p62 downregulation and increased LC3-I to LC3-II conversion. Finally, in vivo findings confirmed that vitexin suppressed tumor growth through activation of autophagic cascade in HCT-116 xenograft model. Taken together, our study insights a probable novel association between HSF-1 and ApoL-1 was established in this study, which supports HSF-1 as a potential target of vitexin to improve treatment outcome in colorectal cancer.

Original languageEnglish (US)
Pages (from-to)112426-112441
Number of pages16
Issue number68
StatePublished - 2017

Bibliographical note

Funding Information:
This research was funded by NRF (National Research Foundation of South Korea)-2016R1A2B4009227 and 2017R1A2B2005629.

Publisher Copyright:
© Bhardwaj et al.


  • ApoL1
  • Autophagic cell death
  • Colorectal carcinoma
  • HSF-1
  • Vitexin


Dive into the research topics of 'Vitexin confers HSF-1 mediated autophagic cell death by activating JNK and ApoL1 in colorectal carcinoma cells'. Together they form a unique fingerprint.

Cite this