We’re switching gears today and moving from detection of flavokavains and kavalactones to another clinical use for them. We’ll be touching upon another use for these chemicals during cancer treatment.
Mucositis:
One of the most common, painful and debilitating treatments of cancer therapy is called oral mucositis. The majority of oral cancer patients will experience some degree of it. This condition occurs during cancer treatments that attack the rapidly dividing epithelial cell lining of the gastro-intestinal tract. Symptoms include swollen gums, blood in the mouth, difficulty swallowing or talking, and open sores in the mouth or on the gums [1]. Currently there are only methods of management of symptoms and no accepted direct treatment for this condition.
Why does this happen?
Cancer treatments are naturally aggressive and while they target cancer cells, they also happen to affect healthy cells as well. This damage is caused by the release of H202 (hydrogen peroxide) also known as "free radicals" or "reactive oxygen species" which causes cellular stress and can lead to cell death. The progression of mucositis has been seen in 5 steps.
How does kava play into this?
Researchers used kavalactones and flavokavains in kava to assess the ability for them to inhibit cellular damage from free radicals that are caused by either radiation or chemical chemotherapy or both. They pre-treated human oral keratinocytes (an epidermal cell which produces keratin) with Flavokavain-A, Flavokavain-B, Methysticin, Kavain, and Yangonin for up to 72 hours [3].
How does this affect me?
In short, currently it doesn’t, however this type of research opens the doors to the creation of drugs that can attempt to tackle some of the most painful side effects of cancer treatment. This research concluded that FKA and kavain have the potential to reduce ROS production in oral mucus cells without harming the cell itself. It also states that kava constituents that demonstrate antioxidative effects and anti-inflammatory effects in the absence of toxic side effects are likely to be of significant use in the treatment of this debilitating condition in the future.
Science marches on.
[1] Mucositis. The Oral Cancer Foundation. (n.d.).
https://oralcancerfoundation.org/complications/mucositis/.
[2] Lalla, Rajesh V., Stephen T. Sonis, and Douglas E. Peterson. 2008. “Management of Oral Mucositis in Patients Who Have Cancer.” Dental Clinics of North America 52 (1): 61–77, viii.
https://doi.org/10.1016/j.cden.2007.10.002.
https://sci-hub.st/10.1016/j.cden.2007.10.002
[3] Yiannis, Callisthenis, Kevin Huang, An Nhien Tran, Cathy Zeng, Emily Dao, Oliver Baselyous, Muaaz Adil Mithwani, et al. 2020. “Protective Effect of Kava Constituents in an in Vitro Model of Oral Mucositis.” Journal of Cancer Research and Clinical Oncology 146 (7): 1801–11.
https://doi.org/10.1007/s00432-020-03253-3.
https://sci-hub.st/10.1007/s00432-020-03253-3
Mucositis:
One of the most common, painful and debilitating treatments of cancer therapy is called oral mucositis. The majority of oral cancer patients will experience some degree of it. This condition occurs during cancer treatments that attack the rapidly dividing epithelial cell lining of the gastro-intestinal tract. Symptoms include swollen gums, blood in the mouth, difficulty swallowing or talking, and open sores in the mouth or on the gums [1]. Currently there are only methods of management of symptoms and no accepted direct treatment for this condition.
Why does this happen?
Cancer treatments are naturally aggressive and while they target cancer cells, they also happen to affect healthy cells as well. This damage is caused by the release of H202 (hydrogen peroxide) also known as "free radicals" or "reactive oxygen species" which causes cellular stress and can lead to cell death. The progression of mucositis has been seen in 5 steps.
- Direct tissue damage to the epithelial cells due to radiation or chemotherapy. This generates ROS or “reactive oxygen species” also known as free-radicals.
- Upregulation of inflammation. Free radicals activate second messengers that lead to cytokine release.
- Upregulation of proinflammatory cytokines that cause damage to mucosal cells.
- Ulceration
- Healing [2]
How does kava play into this?
Researchers used kavalactones and flavokavains in kava to assess the ability for them to inhibit cellular damage from free radicals that are caused by either radiation or chemical chemotherapy or both. They pre-treated human oral keratinocytes (an epidermal cell which produces keratin) with Flavokavain-A, Flavokavain-B, Methysticin, Kavain, and Yangonin for up to 72 hours [3].
- Flavokavain-A: At the dose of 5ug/ml FKA demonstrated a protective antioxidant effect against reactive oxygen species production. There was no significant effect on cell viability, and the protection was able to be attributed to the FKA.
- Flavokavain-B: pre-treatment with 2.5ug/ml FKB indicated a trend of reducing free radicals, however doses over 5ug/ml significantly reduced cell viability and as such FKB had demonstrated a cytotoxic effect. It’s thought that any observed difference in ROS is due to loss of cellular activity and not through antioxidant effects.
- Methysticin: It was not found that methysicin inhibited production of free radicals.
- Kavain: Kavain was shown to have a reducing effect on free radicals in pre-treatment for 24 hours.
- Yangonin: Yangonin was found to have no effect on oxidant production, and even displayed mild cytotoxicity in this study.
How does this affect me?
In short, currently it doesn’t, however this type of research opens the doors to the creation of drugs that can attempt to tackle some of the most painful side effects of cancer treatment. This research concluded that FKA and kavain have the potential to reduce ROS production in oral mucus cells without harming the cell itself. It also states that kava constituents that demonstrate antioxidative effects and anti-inflammatory effects in the absence of toxic side effects are likely to be of significant use in the treatment of this debilitating condition in the future.
Science marches on.
[1] Mucositis. The Oral Cancer Foundation. (n.d.).
https://oralcancerfoundation.org/complications/mucositis/.
[2] Lalla, Rajesh V., Stephen T. Sonis, and Douglas E. Peterson. 2008. “Management of Oral Mucositis in Patients Who Have Cancer.” Dental Clinics of North America 52 (1): 61–77, viii.
https://doi.org/10.1016/j.cden.2007.10.002.
https://sci-hub.st/10.1016/j.cden.2007.10.002
[3] Yiannis, Callisthenis, Kevin Huang, An Nhien Tran, Cathy Zeng, Emily Dao, Oliver Baselyous, Muaaz Adil Mithwani, et al. 2020. “Protective Effect of Kava Constituents in an in Vitro Model of Oral Mucositis.” Journal of Cancer Research and Clinical Oncology 146 (7): 1801–11.
https://doi.org/10.1007/s00432-020-03253-3.
https://sci-hub.st/10.1007/s00432-020-03253-3