Pterostilbene in Cancer Therapy
Natural polyphenols are organic chemicals which contain phenol units in their structures and possess antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene; PT) is a phytoalexin originall...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-03-01
|
| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/10/3/492 |
| _version_ | 1797540589475987456 |
|---|---|
| author | Elena Obrador Rosario Salvador-Palmer Ali Jihad-Jebbar Rafael López-Blanch Thanh H. Dellinger Ryan W. Dellinger José M. Estrela |
| author_facet | Elena Obrador Rosario Salvador-Palmer Ali Jihad-Jebbar Rafael López-Blanch Thanh H. Dellinger Ryan W. Dellinger José M. Estrela |
| author_sort | Elena Obrador |
| collection | DOAJ |
| description | Natural polyphenols are organic chemicals which contain phenol units in their structures and possess antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene; PT) is a phytoalexin originally isolated from the heartwood of red sandalwood. As recently reported by our group, PT was shown to be effective in the treatment of melanoma. Counterintuitively, PT is not effective (cytotoxic) against melanoma in vitro, and only under in vivo conditions does PT display its anticancer activity. This study elucidated that PT can be effective against melanoma through the inhibition of adrenocorticotropic hormone production in the brain of a mouse, which weakens the Nrf2-dependent antioxidant defenses of melanoma and also pancreatic cancers. This results in both the inhibition of tumor growth and sensitization of the tumor to oxidative stress. Moreover, PT can promote cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 content, a known stabilizer of lysosomal membranes. In addition, the safety of PT administered i.v. has been evaluated in mice. PT was found to be pharmacologically safe because it showed no organ-specific or systemic toxicity (including tissue histopathologic examination and regular hematology and clinical chemistry data) even when administered i.v. at a high dose (30 mg/kg per day × 23 days). Moreover, new pharmacological advances are being developed to increase its bioavailability and, thereby, its bioefficacy. Therefore, although applications of PT in cancer therapy are just beginning to be explored, it represents a potential (and effective) adjuvant/sensitizing therapy which may improve the results of various oncotherapies. The aim of this review is to present and discuss the results that in our opinion best support the usefulness of PT in cancer therapy, making special emphasis on the in vivo evidence. |
| first_indexed | 2024-03-10T13:02:24Z |
| format | Article |
| id | doaj.art-df6d36b6df904d9587431c7d30c05079 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T13:02:24Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-df6d36b6df904d9587431c7d30c050792023-11-21T11:24:50ZengMDPI AGAntioxidants2076-39212021-03-0110349210.3390/antiox10030492Pterostilbene in Cancer TherapyElena Obrador0Rosario Salvador-Palmer1Ali Jihad-Jebbar2Rafael López-Blanch3Thanh H. Dellinger4Ryan W. Dellinger5José M. Estrela6Department of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010 Valencia, SpainDepartment of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010 Valencia, SpainDepartment of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010 Valencia, SpainDepartment of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010 Valencia, SpainDepartment of Surgery, Division of Gynecologic Surgery, City of Hope, 1500 East Duarte Rd, Duarte, CA 91010, USAElysium Health Inc., 434 Broadway, New York, NY 10013, USADepartment of Physiology, Faculty of Medicine and Odontology, University of Valencia, 15 Av. Blasco Ibañez, 46010 Valencia, SpainNatural polyphenols are organic chemicals which contain phenol units in their structures and possess antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene; PT) is a phytoalexin originally isolated from the heartwood of red sandalwood. As recently reported by our group, PT was shown to be effective in the treatment of melanoma. Counterintuitively, PT is not effective (cytotoxic) against melanoma in vitro, and only under in vivo conditions does PT display its anticancer activity. This study elucidated that PT can be effective against melanoma through the inhibition of adrenocorticotropic hormone production in the brain of a mouse, which weakens the Nrf2-dependent antioxidant defenses of melanoma and also pancreatic cancers. This results in both the inhibition of tumor growth and sensitization of the tumor to oxidative stress. Moreover, PT can promote cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 content, a known stabilizer of lysosomal membranes. In addition, the safety of PT administered i.v. has been evaluated in mice. PT was found to be pharmacologically safe because it showed no organ-specific or systemic toxicity (including tissue histopathologic examination and regular hematology and clinical chemistry data) even when administered i.v. at a high dose (30 mg/kg per day × 23 days). Moreover, new pharmacological advances are being developed to increase its bioavailability and, thereby, its bioefficacy. Therefore, although applications of PT in cancer therapy are just beginning to be explored, it represents a potential (and effective) adjuvant/sensitizing therapy which may improve the results of various oncotherapies. The aim of this review is to present and discuss the results that in our opinion best support the usefulness of PT in cancer therapy, making special emphasis on the in vivo evidence.https://www.mdpi.com/2076-3921/10/3/492pterostilbenepolyphenolsstilbenescanceroxidative stressheat-shock proteins |
| spellingShingle | Elena Obrador Rosario Salvador-Palmer Ali Jihad-Jebbar Rafael López-Blanch Thanh H. Dellinger Ryan W. Dellinger José M. Estrela Pterostilbene in Cancer Therapy Antioxidants pterostilbene polyphenols stilbenes cancer oxidative stress heat-shock proteins |
| title | Pterostilbene in Cancer Therapy |
| title_full | Pterostilbene in Cancer Therapy |
| title_fullStr | Pterostilbene in Cancer Therapy |
| title_full_unstemmed | Pterostilbene in Cancer Therapy |
| title_short | Pterostilbene in Cancer Therapy |
| title_sort | pterostilbene in cancer therapy |
| topic | pterostilbene polyphenols stilbenes cancer oxidative stress heat-shock proteins |
| url | https://www.mdpi.com/2076-3921/10/3/492 |
| work_keys_str_mv | AT elenaobrador pterostilbeneincancertherapy AT rosariosalvadorpalmer pterostilbeneincancertherapy AT alijihadjebbar pterostilbeneincancertherapy AT rafaellopezblanch pterostilbeneincancertherapy AT thanhhdellinger pterostilbeneincancertherapy AT ryanwdellinger pterostilbeneincancertherapy AT josemestrela pterostilbeneincancertherapy |