Gathering good data from bad studies.

[mlenny]

I only share this for an open discussion because I see multiple things wrong with this study. Namely, they used HepG2 cells, which are a cancer cell line. Cancer cells are obviously not normal cells. The mechanism of injury it says is apoptosis ("cell suicide"), which is desirable and normal for cells with genome damage. Couldn't it well be that these compounds target only malignant cells, which would be a *positive* thing that gives it a potential place in cancer treatment?

Matthew

Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro - PubMed

While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved...

pubmed.ncbi.nlm.nih.gov

 

[The Kap'n]

I only share this for an open discussion because I see multiple things wrong with this study. Namely, they used HepG2 cells, which are a cancer cell line. Cancer cells are obviously not normal cells. The mechanism of injury it says is apoptosis ("cell suicide"), which is desirable and normal for cells with genome damage. Couldn't it well be that these compounds target only malignant cells, which would be a *positive* thing that gives it a potential place in cancer treatment?

Matthew

Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro - PubMed

While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved...

pubmed.ncbi.nlm.nih.gov

Keep an eye on your concentration levels here. They're using 200µm which is in another universe in terms of systemic circulations. The highest plasma level ever recorded was 17µm. The vast majority of these studies use concentration amounts that we could never realistically hit with kava consumption in any form.

Here's a sampling of other cancer related kava studies:

Celentano, Antonio, Callisthenis Yiannis, Rita Paolini, Pangzhen Zhang, Camile S. Farah, Nicola Cirillo, Tami Yap, and Michael McCullough. 2020. “Kava Constituents Exert Selective Anticancer Effects in Oral Squamous Cell Carcinoma Cells in Vitro.” Scientific Reports 10 (1): 1–11. https://doi.org/10.1038/s41598-020-73058-4.

Einbond, L. S., A. Negrin, D. M. Kulakowski, H-A Wu, V. Antonetti, F. Jalees, W. Law, et al. 2017. “Traditional Preparations of Kava (Piper Methysticum) Inhibit the Growth of Human Colon Cancer Cells in Vitro.” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 24 (January): 1–13. https://doi.org/10.1016/j.phymed.2016.11.002.

Hu, Qi, Pedro Corral, Sreekanth C. Narayanapillai, Pablo Leitzman, Pramod Upadhyaya, M. Gerard O’Sullivan, Stephen S. Hecht, Junxuan Lu, and Chengguo Xing. 2020. “Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.” Chemical Research in Toxicology 33 (7): 1980–88. https://doi.org/10.1021/acs.chemrestox.0c00161.

Jandial, Danielle D., Lauren S. Krill, Lixia Chen, Chunli Wu, Yu Ke, Jun Xie, Bang H. Hoang, and Xiaolin Zi. 2017. “Induction of G2M Arrest by Flavokawain A, a Kava Chalcone, Increases the Responsiveness of HER2-Overexpressing Breast Cancer Cells to Herceptin.” Molecules 22 (3). https://doi.org/10.3390/molecules22030462.

Li, Xuesen, Liankun Song, Shan Xu, Matthew Tippin, Shuan Meng, Jun Xie, Edward Uchio, and Xiaolin Zi. 2021. “Kava Root Extracts Hinder Prostate Cancer Development and Tumorigenesis by Involvement of Dual Inhibition of MAO-A and LSD1.” Journal of Translational Genetics and Genomics 5 (May): 163–72. https://doi.org/10.20517/jtgg.2021.22.

Liu, Zhongbo, U-Syn Ha, Ke Yu, Chunli Wu, Noriko Yokoyama, and Xiaolin Zi. 2017. “Kavalactone Yangonin Induces Autophagy and Sensitizes Bladder Cancer Cells to Flavokawain A and Docetaxel via Inhibition of the mTOR Pathway.” Journal of Biomedical Research 31 (5): 408–18. https://doi.org/10.7555/JBR.31.20160160.

Phang, Chung-Weng, Sri Nurestri Abd Malek, and Saiful Anuar Karsani. 2021. “Flavokawain C Exhibits Anti-Tumor Effects on in Vivo HCT 116 Xenograft and Identification of Its Apoptosis-Linked Serum Biomarkers via Proteomic Analysis.” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 137 (May): 110846. https://doi.org/10.1016/j.biopha.2020.110846.

Puppala M, Narayanapillai SC, Leitzman P, Sun H, Upadhyaya P, O’Sullivan MG, Hecht SS, Xing C. 2017. “Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced O 6-Methylguanine and Lung Tumor in A/J Mice.” Journal of Medicinal Chemistry 28 (60): 7935–40. https://doi.org/10.1021/acs.jmedchem.7b00921.

Walia, Arman, Nikta Rezakahn Khajeh, Michael Wu, Cyrus Khoyilar, and Xiaolin Zi. 2016. “Kava in Prostate Cancer Prevention and Treatment.” Complementary and Alternative Medicines in Prostate Cancer: A Comprehensive Approach, 29. https://books.google.com/books?hl=e...ts=h2uT5AX3HE&sig=oVdsZoh3Km_u658jMLuJtAcfB64.

 

[mlenny]

Keep an eye on your concentration levels here. They're using 200µm which is in another universe in terms of systemic circulations. The highest plasma level ever recorded was 17µm. The vast majority of these studies use concentration amounts that we could never realistically hit with kava consumption in any form.

Here's a sampling of other cancer related kava studies:

Celentano, Antonio, Callisthenis Yiannis, Rita Paolini, Pangzhen Zhang, Camile S. Farah, Nicola Cirillo, Tami Yap, and Michael McCullough. 2020. “Kava Constituents Exert Selective Anticancer Effects in Oral Squamous Cell Carcinoma Cells in Vitro.” Scientific Reports 10 (1): 1–11. https://doi.org/10.1038/s41598-020-73058-4.

Einbond, L. S., A. Negrin, D. M. Kulakowski, H-A Wu, V. Antonetti, F. Jalees, W. Law, et al. 2017. “Traditional Preparations of Kava (Piper Methysticum) Inhibit the Growth of Human Colon Cancer Cells in Vitro.” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 24 (January): 1–13. https://doi.org/10.1016/j.phymed.2016.11.002.

Hu, Qi, Pedro Corral, Sreekanth C. Narayanapillai, Pablo Leitzman, Pramod Upadhyaya, M. Gerard O’Sullivan, Stephen S. Hecht, Junxuan Lu, and Chengguo Xing. 2020. “Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.” Chemical Research in Toxicology 33 (7): 1980–88. https://doi.org/10.1021/acs.chemrestox.0c00161.

Jandial, Danielle D., Lauren S. Krill, Lixia Chen, Chunli Wu, Yu Ke, Jun Xie, Bang H. Hoang, and Xiaolin Zi. 2017. “Induction of G2M Arrest by Flavokawain A, a Kava Chalcone, Increases the Responsiveness of HER2-Overexpressing Breast Cancer Cells to Herceptin.” Molecules 22 (3). https://doi.org/10.3390/molecules22030462.

Li, Xuesen, Liankun Song, Shan Xu, Matthew Tippin, Shuan Meng, Jun Xie, Edward Uchio, and Xiaolin Zi. 2021. “Kava Root Extracts Hinder Prostate Cancer Development and Tumorigenesis by Involvement of Dual Inhibition of MAO-A and LSD1.” Journal of Translational Genetics and Genomics 5 (May): 163–72. https://doi.org/10.20517/jtgg.2021.22.

Liu, Zhongbo, U-Syn Ha, Ke Yu, Chunli Wu, Noriko Yokoyama, and Xiaolin Zi. 2017. “Kavalactone Yangonin Induces Autophagy and Sensitizes Bladder Cancer Cells to Flavokawain A and Docetaxel via Inhibition of the mTOR Pathway.” Journal of Biomedical Research 31 (5): 408–18. https://doi.org/10.7555/JBR.31.20160160.

Phang, Chung-Weng, Sri Nurestri Abd Malek, and Saiful Anuar Karsani. 2021. “Flavokawain C Exhibits Anti-Tumor Effects on in Vivo HCT 116 Xenograft and Identification of Its Apoptosis-Linked Serum Biomarkers via Proteomic Analysis.” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 137 (May): 110846. https://doi.org/10.1016/j.biopha.2020.110846.

Puppala M, Narayanapillai SC, Leitzman P, Sun H, Upadhyaya P, O’Sullivan MG, Hecht SS, Xing C. 2017. “Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced O 6-Methylguanine and Lung Tumor in A/J Mice.” Journal of Medicinal Chemistry 28 (60): 7935–40. https://doi.org/10.1021/acs.jmedchem.7b00921.

Walia, Arman, Nikta Rezakahn Khajeh, Michael Wu, Cyrus Khoyilar, and Xiaolin Zi. 2016. “Kava in Prostate Cancer Prevention and Treatment.” Complementary and Alternative Medicines in Prostate Cancer: A Comprehensive Approach, 29. https://books.google.com/books?hl=e...ts=h2uT5AX3HE&sig=oVdsZoh3Km_u658jMLuJtAcfB64.

I didn't even notice that part. But if you tested cyclophosphamide in a cancer cell line, you'd see of the charts toxicity. But that's what you would want to see.

Matthew

 

[The Kap'n]

I didn't even notice that part. But if you tested cyclophosphamide in a cancer cell line, you'd see of the charts toxicity. But that's what you would want to see.

Matthew

Essentially yes, with most chemotherapies of this type the name of the game is killing, and they're usually only somewhat specific in what they kill, so you end up being sickened from the excess apoptosis that happens as a side effect.

Also I missed part of your original post. HEPG2 cells aren't necessarily that of an oncogenic line. They are simply hepatocytes frozen from a human source. No cancer topics involved in that study.

 

[Alia]

By now there are reams of studies of all sorts which demonstrate kava and cancer prevention and cancer cell death.
I like best the idea that drinking some kava everyday may help keep us safe in many ways!
Most all this started when it was noticed that places such as Vanuatu, Fiji, Samoa had low rates of cancer and high
rates of smoking. In one of the earlier UM studies, a poster was generated with the following comment:
"Kava consumption inversely correlates with cancer incidence, suggesting that kava has chemopreventive properties".
With it is a chart showing cancer rates with Hawai'i being very high and Vanuatu being very low.
Much more kava consumed there than here is the take away.

 

[mlenny]

Essentially yes, with most chemotherapies of this type the name of the game is killing, and they're usually only somewhat specific in what they kill, so you end up being sickened from the excess apoptosis that happens as a side effect.

Also I missed part of your original post. HEPG2 cells aren't necessarily that of an oncogenic line. They are simply hepatocytes frozen from a human source. No cancer topics involved in that study.

https://www.atcc.org/products/hb-8065

What I've seen says it's a cancer cell line, anyway, which makes the data virtually useless and possibly highly deceptive in this case.

 

[The Kap'n]

https://www.atcc.org/products/hb-8065

What I've seen says it's a cancer cell line, anyway, which makes the data virtually useless and possibly highly deceptive in this case.

I stand corrected there. You're right about that . It's a non-tumorigenic line with high proliferation rates which makes them better candidates for culturing and study.

The paper itself was not concentrated on cancer. The reason they use HEPG2 cells is that this cell line is the most commonly used in drug metabolism and hepatotoxicity studies. It may not be exactly the type of liver cells we have in vivo, but it is an accepted host for ascertaining certain functions of compounds.

Here's a little study on it:

Donato, María Teresa, Laia Tolosa, and María José Gómez-Lechón. 2015. “Culture and Functional Characterization of Human Hepatoma HepG2 Cells.” Methods in Molecular Biology 1250: 77–93. https://sci-hub.se/https://doi.org/10.1007/978-1-4939-2074-7_5

 

[Jack3]

Keep an eye on your concentration levels here. They're using 200µm which is in another universe in terms of systemic circulations. The highest plasma level ever recorded was 17µm. The vast majority of these studies use concentration amounts that we could never realistically hit with kava consumption in any form.

Here's a sampling of other cancer related kava studies:

Celentano, Antonio, Callisthenis Yiannis, Rita Paolini, Pangzhen Zhang, Camile S. Farah, Nicola Cirillo, Tami Yap, and Michael McCullough. 2020. “Kava Constituents Exert Selective Anticancer Effects in Oral Squamous Cell Carcinoma Cells in Vitro.” Scientific Reports 10 (1): 1–11. https://doi.org/10.1038/s41598-020-73058-4.

Einbond, L. S., A. Negrin, D. M. Kulakowski, H-A Wu, V. Antonetti, F. Jalees, W. Law, et al. 2017. “Traditional Preparations of Kava (Piper Methysticum) Inhibit the Growth of Human Colon Cancer Cells in Vitro.” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 24 (January): 1–13. https://doi.org/10.1016/j.phymed.2016.11.002.

Hu, Qi, Pedro Corral, Sreekanth C. Narayanapillai, Pablo Leitzman, Pramod Upadhyaya, M. Gerard O’Sullivan, Stephen S. Hecht, Junxuan Lu, and Chengguo Xing. 2020. “Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.” Chemical Research in Toxicology 33 (7): 1980–88. https://doi.org/10.1021/acs.chemrestox.0c00161.

Jandial, Danielle D., Lauren S. Krill, Lixia Chen, Chunli Wu, Yu Ke, Jun Xie, Bang H. Hoang, and Xiaolin Zi. 2017. “Induction of G2M Arrest by Flavokawain A, a Kava Chalcone, Increases the Responsiveness of HER2-Overexpressing Breast Cancer Cells to Herceptin.” Molecules 22 (3). https://doi.org/10.3390/molecules22030462.

Li, Xuesen, Liankun Song, Shan Xu, Matthew Tippin, Shuan Meng, Jun Xie, Edward Uchio, and Xiaolin Zi. 2021. “Kava Root Extracts Hinder Prostate Cancer Development and Tumorigenesis by Involvement of Dual Inhibition of MAO-A and LSD1.” Journal of Translational Genetics and Genomics 5 (May): 163–72. https://doi.org/10.20517/jtgg.2021.22.

Liu, Zhongbo, U-Syn Ha, Ke Yu, Chunli Wu, Noriko Yokoyama, and Xiaolin Zi. 2017. “Kavalactone Yangonin Induces Autophagy and Sensitizes Bladder Cancer Cells to Flavokawain A and Docetaxel via Inhibition of the mTOR Pathway.” Journal of Biomedical Research 31 (5): 408–18. https://doi.org/10.7555/JBR.31.20160160.

Phang, Chung-Weng, Sri Nurestri Abd Malek, and Saiful Anuar Karsani. 2021. “Flavokawain C Exhibits Anti-Tumor Effects on in Vivo HCT 116 Xenograft and Identification of Its Apoptosis-Linked Serum Biomarkers via Proteomic Analysis.” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 137 (May): 110846. https://doi.org/10.1016/j.biopha.2020.110846.

Puppala M, Narayanapillai SC, Leitzman P, Sun H, Upadhyaya P, O’Sullivan MG, Hecht SS, Xing C. 2017. “Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced O 6-Methylguanine and Lung Tumor in A/J Mice.” Journal of Medicinal Chemistry 28 (60): 7935–40. https://doi.org/10.1021/acs.jmedchem.7b00921.

Walia, Arman, Nikta Rezakahn Khajeh, Michael Wu, Cyrus Khoyilar, and Xiaolin Zi. 2016. “Kava in Prostate Cancer Prevention and Treatment.” Complementary and Alternative Medicines in Prostate Cancer: A Comprehensive Approach, 29. https://books.google.com/books?hl=e...ts=h2uT5AX3HE&sig=oVdsZoh3Km_u658jMLuJtAcfB64.

I would like to have access to all studies that conclude kava has therapeutic value in any area.

 

[The Kap'n]

I would like to have access to all studies that conclude kava has therapeutic value in any area.

Check your messages

 

[JohnMichael]

Keep an eye on your concentration levels here. They're using 200µm which is in another universe in terms of systemic circulations. The highest plasma level ever recorded was 17µm. The vast majority of these studies use concentration amounts that we could never realistically hit with kava consumption in any form.

Here's a sampling of other cancer related kava studies:

Celentano, Antonio, Callisthenis Yiannis, Rita Paolini, Pangzhen Zhang, Camile S. Farah, Nicola Cirillo, Tami Yap, and Michael McCullough. 2020. “Kava Constituents Exert Selective Anticancer Effects in Oral Squamous Cell Carcinoma Cells in Vitro.” Scientific Reports 10 (1): 1–11. https://doi.org/10.1038/s41598-020-73058-4.

Einbond, L. S., A. Negrin, D. M. Kulakowski, H-A Wu, V. Antonetti, F. Jalees, W. Law, et al. 2017. “Traditional Preparations of Kava (Piper Methysticum) Inhibit the Growth of Human Colon Cancer Cells in Vitro.” Phytomedicine: International Journal of Phytotherapy and Phytopharmacology 24 (January): 1–13. https://doi.org/10.1016/j.phymed.2016.11.002.

Hu, Qi, Pedro Corral, Sreekanth C. Narayanapillai, Pablo Leitzman, Pramod Upadhyaya, M. Gerard O’Sullivan, Stephen S. Hecht, Junxuan Lu, and Chengguo Xing. 2020. “Oral Dosing of Dihydromethysticin Ahead of Tobacco Carcinogen NNK Effectively Prevents Lung Tumorigenesis in A/J Mice.” Chemical Research in Toxicology 33 (7): 1980–88. https://doi.org/10.1021/acs.chemrestox.0c00161.

Jandial, Danielle D., Lauren S. Krill, Lixia Chen, Chunli Wu, Yu Ke, Jun Xie, Bang H. Hoang, and Xiaolin Zi. 2017. “Induction of G2M Arrest by Flavokawain A, a Kava Chalcone, Increases the Responsiveness of HER2-Overexpressing Breast Cancer Cells to Herceptin.” Molecules 22 (3). https://doi.org/10.3390/molecules22030462.

Li, Xuesen, Liankun Song, Shan Xu, Matthew Tippin, Shuan Meng, Jun Xie, Edward Uchio, and Xiaolin Zi. 2021. “Kava Root Extracts Hinder Prostate Cancer Development and Tumorigenesis by Involvement of Dual Inhibition of MAO-A and LSD1.” Journal of Translational Genetics and Genomics 5 (May): 163–72. https://doi.org/10.20517/jtgg.2021.22.

Liu, Zhongbo, U-Syn Ha, Ke Yu, Chunli Wu, Noriko Yokoyama, and Xiaolin Zi. 2017. “Kavalactone Yangonin Induces Autophagy and Sensitizes Bladder Cancer Cells to Flavokawain A and Docetaxel via Inhibition of the mTOR Pathway.” Journal of Biomedical Research 31 (5): 408–18. https://doi.org/10.7555/JBR.31.20160160.

Phang, Chung-Weng, Sri Nurestri Abd Malek, and Saiful Anuar Karsani. 2021. “Flavokawain C Exhibits Anti-Tumor Effects on in Vivo HCT 116 Xenograft and Identification of Its Apoptosis-Linked Serum Biomarkers via Proteomic Analysis.” Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie 137 (May): 110846. https://doi.org/10.1016/j.biopha.2020.110846.

Puppala M, Narayanapillai SC, Leitzman P, Sun H, Upadhyaya P, O’Sullivan MG, Hecht SS, Xing C. 2017. “Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone-Induced O 6-Methylguanine and Lung Tumor in A/J Mice.” Journal of Medicinal Chemistry 28 (60): 7935–40. https://doi.org/10.1021/acs.jmedchem.7b00921.

Walia, Arman, Nikta Rezakahn Khajeh, Michael Wu, Cyrus Khoyilar, and Xiaolin Zi. 2016. “Kava in Prostate Cancer Prevention and Treatment.” Complementary and Alternative Medicines in Prostate Cancer: A Comprehensive Approach, 29. https://books.google.com/books?hl=e...ts=h2uT5AX3HE&sig=oVdsZoh3Km_u658jMLuJtAcfB64.

Nice list. The fifth link down the list on prostate cancer was interesting because they not only tested kava on very early stage prostate cancer, but also on late stage with large prostate tumors in mice. This quote: "The mean GU weight of the mice fed with 0.6% KRE containing food was significantly reduced when compared to the control group (Figure 2A; 1.98 g ± 2.07 g vs. 3.63 g ± 4.28 g; P < 0.05; Mann-Whitney U and Kolmogorov-Smirnov test). The percentages of large tumors (GU weight > 0.9 g) were also decreased from 86.4% in the control group to 52.2% and 43.5% in 0.3% and 0.6% KRE food groups, respectively [Figure 2B]." That's really significant.

 

[Orz[EST]]

Age-correlated cancer levels or cancer levels?

Usually in 3rd world countries people die before they get a chance to get cancer or neurodegenerative disease.

Prostate tumor is more often than not like a chronic nonlethal treatable disease nowadays. Of course, sometimes it requires surgery and that is not that mild, of course.

 

[The Kap'n]

I only share this for an open discussion because I see multiple things wrong with this study. Namely, they used HepG2 cells, which are a cancer cell line. Cancer cells are obviously not normal cells. The mechanism of injury it says is apoptosis ("cell suicide"), which is desirable and normal for cells with genome damage. Couldn't it well be that these compounds target only malignant cells, which would be a *positive* thing that gives it a potential place in cancer treatment?

Matthew

Kavalactones Yangonin and Methysticin induce apoptosis in human hepatocytes (HepG2) in vitro - PubMed

While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved...

pubmed.ncbi.nlm.nih.gov

I've been keeping this in mind as I continue my research on kava, and I think you're on to something more fundamental here than I first thought. Some of these conclusions may be quite incorrect based on studies in cancer lines. Specifically AhR studies, and CYP1A1 induction studies.

I'm not smart enough to connect all the dots just yet, but I'm working my way there.