Photodynamic therapy in colorectal cancer treatment—The state of the art in preclinical research

Kawczyk‐Krupka, Aleksandra; Bugaj, Andrzej M.; Latos, Wojciech; Zaremba, Katarzyna; Wawrzyniec, Katarzyna; Kucharzewski, Marek; Sieroń, Aleksander

doi:10.1016/j.pdpdt.2015.07.175

Cited by 60 publications

(62 citation statements)

References 117 publications

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“…Preclinical research on photosensitizers for CRC treatment has captured increased attention in 2016 [30], particularly that this cancer represents the third most common cancer worldwide in men and the second in women (10.0 and 9.2% of the total incidences, respectively) [31]. Human CRC cell line models have recently demonstrated increased resemblance to the corresponding tumor biology in patients as well as important pharmacological utility in preclinical research (including photosensitizer drugs) [32, 33].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, the human CRC lines are representative of the main subtypes of primary tumors at the genomic level, further validating their utility as tools to investigate CRC biology and drug responses [33]. Among the CRC cell lines, HT-29 and HCT 116 have been the most widely investigated models in PDT research [30], and HT-29 is known to be resistant to HY-PDT [10]. …”

Section: Discussionmentioning

confidence: 99%

“…Preclinical research on photosensitizers has captured increased attention very recently, particularly for CRC treatment, as this cancer is known to be resistant to PDT [30]. In this study, we attempted to overcome CRC cell resistance to HY-PDT by pretreatment with HDACis especially that the latter are non-genotoxic agents and can epigenetically sensitize cells to external stimuli.…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, specific HDACis were tested in each group based on the criterion that they be in clinical use or trials and that they manifest a generally favorable toxicity profile [19–21]. The target CRC cell models selected were HCT 116, HCT 116 p53−/−, and HT-29 because they are the most widely investigated cell lines in PDT research [30], and HT-29 is known to be resistant to HY-PDT [10]. We hypothesized that chromatin regulation by HDACis, particularly at the CDKN1A tumor suppressor gene, could sensitize cancer cells to photochemical and photobiological processes induced by HY-PDT.…”

Section: Methodsmentioning

confidence: 99%

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Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A

et al. 2017

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BackgroundHypericin-mediated photodynamic therapy (HY-PDT) has recently captured increased attention as an alternative minimally invasive anticancer treatment, although cancer cells may acquire resistance. Therefore, combination treatments may be necessary to enhance HY-PDT efficacy. Histone deacetylase inhibitors (HDACis) are often used in combination treatments due to their non-genotoxic properties and epigenetic potential to sensitize cells to external stimuli. Therefore, this study attempts for the first time to investigate the therapeutic effects of HDACis in combination with visible light-mediated PDT against cancer. Specifically, the colorectal cancer cell model was used due to its known resistance to HY-PDT.ResultsTwo chemical groups of HDACis were tested in combination with HY-PDT: the hydroxamic acids Saha and Trichostatin A, and the short-chain fatty acids valproic acid and sodium phenylbutyrate (NaPB), as inhibitors of all-class versus nuclear HDACs, respectively. The selected HDACis manifest a favorable clinical toxicity profile and showed similar potencies and mechanisms in intragroup comparisons but different biological effects in intergroup analyses. HDACi combination with HY-PDT significantly attenuated cancer cell resistance to treatment and caused the two HDACi groups to become similarly potent. However, the short-chain fatty acids, in combination with HY-PDT, showed increased selectivity towards inhibition of HDACs versus other key epigenetic enzymes, and NaPB induced the strongest expression of the otherwise silenced tumor suppressor CDKN1A, a hallmark gene for HDACi-mediated chromatin modulation. Epigenetic regulation of CDKN1A by NaPB was associated with histone acetylation at enhancer and promoter elements rather than histone or DNA methylation at those or other regulatory regions of this gene. Moreover, NaPB, compared to the other HDACis, caused milder effects on global histone acetylation, suggesting a more specific effect on CDKN1A chromatin architecture relative to global chromatin structure. The mechanism of NaPB + HY-PDT was P53-dependent and likely driven by the HY-PDT rather than the NaPB constituent.ConclusionsOur results show that HDACis potentiate the antitumor efficacy of HY-PDT in colorectal cancer cells, overcoming their resistance to this drug and epigenetically reactivating the expression of CDKN1A. Besides their therapeutic potential, hypericin and these HDACis are non-genotoxic constituents of dietary agents, hence, represent interesting targets for investigating mechanisms of dietary-based cancer prevention.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0359-x) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A

et al. 2017

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“…[2,3] Photodynamic therapy depends on breaking down of the cancerous tissues by a photosensitizer compound. [4] When the photosensitizer compound irradiated by light, singlet oxygen is formed as a result of energy transfers. This singlet oxygen can break down the cancerous tissues and prevent division of cancerous cells.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization, Photophysical and Photochemical Properties of Novel Phthalocyanines

Demirbaş

2020

ChemistrySelect

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The benzothiazole substituted phthalonitrile (3) and nonperipherally tetra benzothiazole substituted metal-free (4), zinc (II) (5) and lead(II) phthalocyanine (6) complexes were prepared. The compounds (3-6) were characterized by IR, NMR, UV-Vis and mass spectroscopy data. After synthesis, photochemical and photophysical parameters of the compounds (4-6) were analyzed to determine photosensitizer performance of them for PDT applications. Firstly, the most suitable solvent for compounds (4-6) was found by aggregation studies. Then, fluorescence properties were measured in DMF at 1x10 À 6 M. Singlet oxygen properties were measured in DMF by using 1,3diphenylisobenzofuran (DPBF) as a singlet oxygen quencher. Photodegradation properties were measured under light irradiation in DMF at 1x10 À 5 M. The zinc(II) phthalocyanine (5) had the highest singlet oxygen production capacity (Φ~= 0.62), fluorescence (Φ F = 0.25) and photodegradation quantum yield (Φ d = 3.28x10-4). The results showed that zinc(II) phthalocyanine (5) has potential for photodynamic therapy applications.

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In Vivo Photodynamic Therapy With a Lipophilic Zinc(II) Phthalocyanine Inhibits Colorectal Cancer and Induces a Th1/CD8 Antitumor Immune Response

et al. 2020

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Photodynamic therapy in colorectal cancer treatment—The state of the art in preclinical research

Cited by 60 publications

References 117 publications

Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A

Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A

Synthesis, Characterization, Photophysical and Photochemical Properties of Novel Phthalocyanines

In Vivo Photodynamic Therapy With a Lipophilic Zinc(II) Phthalocyanine Inhibits Colorectal Cancer and Induces a Th1/CD8 Antitumor Immune Response

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