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Updated: Oct 15, 2025

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Protein Kinase A-Mediated Effects of Protein Kinase C Partial Agonist 5-(Hydroxymethyl)Isophthalate 1a3 in Colorectal

Ilari Tarvainen1, Rebecca C Nunn2, Raimo K Tuominen2

  • 1Drug Research Program and Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Finland (I.T., R.C.N., R.K.T., M.H.J., V.T.) ilari.tarvainen@helsinki.fi.

The Journal of Pharmacology and Experimental Therapeutics
|October 26, 2021
PubMed

Insights

A novel compound, 5-(hydroxymethyl)isophthalate 1a3 (HMI-1a3), shows anticancer effects on colorectal cancer cells by activating the cAMP/PKA pathway, not protein kinase C (PKC). This discovery offers new therapeutic strategies for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Colorectal cancer (CRC) presents a significant global health challenge with a growing incidence and mortality rate.
  • There is a critical need for novel anticancer agents with distinct mechanisms of action to combat cancer effectively.
  • Protein kinase C (PKC)-modulating isophthalic acid derivatives have shown promise in preclinical cancer models.

Purpose of the Study:

  • To investigate the anticancer effects of 5-(hydroxymethyl)isophthalate 1a3 (HMI-1a3) on colorectal cancer cell lines.
  • To elucidate the mechanism of action underlying HMI-1a3's cytotoxic effects in colorectal cancer.
  • To explore the potential of HMI-1a3 as a therapeutic agent for colorectal cancer and other malignancies.

Main Methods:

  • Treatment of colorectal cancer cell lines (Caco-2, Colo205, HT29) with HMI-1a3.
  • Assessment of cell proliferation, viability, and apoptosis induction.
  • Serine/threonine kinome profiling and pharmacological kinase inhibitors to identify signaling pathways involved.

Main Results:

  • HMI-1a3 demonstrated significant inhibition of cell proliferation and decreased cell viability in all tested colorectal cancer cell lines.
  • HMI-1a3 induced apoptosis in colorectal cancer cells, indicating a cytotoxic effect.
  • The anticancer activity of HMI-1a3 was found to be independent of protein kinase C (PKC) but mediated through the activation of the cAMP/PKA pathway.

Conclusions:

  • 5-(hydroxymethyl)isophthalate 1a3 (HMI-1a3) exhibits potent anticancer activity against colorectal cancer cell lines.
  • The mechanism of action involves the activation of the cAMP/PKA pathway, representing a novel therapeutic target.
  • HMI-1a3 holds promise as a potential anticancer agent, warranting further investigation for various cancer types and the development of related modulators.

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