Hemin may be useful as prodrug for prostate cancer. It strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells

[Graham49]

Only an invitro study but Hemin is already used to treat acute porphyria. “Given that hemin has been safely administered as a daily infusion at doses ranging from 1 to 4 mg/kg for 3 to 14 days in the treatment of porphyria [32], it holds significant promise for drug development.”

Anticancer Effect of Hemin through ANO1 Inhibition in Human Prostate Cancer Cells

by So-Hyeon Park 1,†ORCID, Yechan Lee 1,†ORCID, Hyejin Jeon 1ORCID, Junghwan Park 1, Jieun Kim 2, Mincheol Kang 2 and Wan Namkung 1,2,*ORCID

Int. J. Mol. Sci. 2024, 25(11), 6032; doi.org/10.3390/ijms25116032

Submission received: 15 April 2024 / Revised: 25 May 2024 / Accepted: 29 May 2024 / Published: 30 May 2024

(This article belongs to the Special Issue Molecular Research on Prostate Cancer)

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Abstract

Anoctamin1 (ANO1), a calcium-activated chloride channel, is overexpressed in a variety of cancer cells, including prostate cancer, and is involved in cancer cell proliferation, migration, and invasion. Inhibition of ANO1 in these cancer cells exhibits anticancer effects. In this study, we conducted a screening to identify novel ANO1 inhibitors with anticancer effects using PC-3 human prostate carcinoma cells. Screening of 2978 approved and investigational drugs revealed that hemin is a novel ANO1 inhibitor with an IC50 value of 0.45 μM. Notably, hemin had no significant effect on intracellular calcium signaling and cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP (cAMP)-regulated chloride channel, and it showed a weak inhibitory effect on ANO2 at 3 μM, a concentration that completely inhibits ANO1. Interestingly, hemin also significantly decreased ANO1 protein levels and strongly inhibited the cell proliferation and migration of PC-3 cells in an ANO1-dependent manner. Furthermore, it strongly induced caspase-3 activation, PARP degradation, and apoptosis in PC-3 cells. These findings suggest that hemin possesses anticancer properties via ANO1 inhibition and could be considered for development as a novel treatment for prostate cancer.

[FRTHBST]

Hmmm, caspase -3 activation, perhaps it could be used with IV-C.